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Find video protocols related to scientific articles indexed in Pubmed.
Guidelines for the diagnosis, prevention and management of implantable cardiac electronic device infection. Report of a joint Working Party project on behalf of the British Society for Antimicrobial Chemotherapy (BSAC, host organization), British Heart Rhythm Society (B
J. Antimicrob. Chemother.
PUBLISHED: 10-31-2014
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Infections related to implantable cardiac electronic devices (ICEDs), including pacemakers, implantable cardiac defibrillators and cardiac resynchronization therapy devices, are increasing in incidence in the USA and are likely to increase in the UK, because more devices are being implanted. These devices have both intravascular and extravascular components and infection can involve the generator, device leads and native cardiac structures or various combinations. ICED infections can be life-threatening, particularly when associated with endocardial infection, and all-cause mortality of up to 35% has been reported. Like infective endocarditis, ICED infections can be difficult to diagnose and manage. This guideline aims to (i) improve the quality of care provided to patients with ICEDs, (ii) provide an educational resource for all relevant healthcare professionals, (iii) encourage a multidisciplinary approach to ICED infection management, (iv) promote a standardized approach to the diagnosis, management, surveillance and prevention of ICED infection through pragmatic evidence-rated recommendations, and (v) advise on future research projects/audit. The guideline is intended to assist in the clinical care of patients with suspected or confirmed ICED infection in the UK, to inform local infection prevention and treatment policies and guidelines and to be used in the development of educational and training material by the relevant professional societies. The questions covered by the guideline are presented at the beginning of each section.
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Sex differences in cardiovascular outcome during progression of aortic valve stenosis.
Heart
PUBLISHED: 10-09-2014
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Women with severe aortic valve stenosis (AS) have better LV systolic function and more concentric LV geometry than their male counterparts. However, sex differences in cardiovascular (CV) outcome during progression of AS have not been reported from a longitudinal prospective study.
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Transcriptional diversity during lineage commitment of human blood progenitors.
Science
PUBLISHED: 09-27-2014
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Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.
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Defining the role of common variation in the genomic and biological architecture of adult human height.
Andrew R Wood, Tonu Esko, Jian Yang, Sailaja Vedantam, Tune H Pers, Stefan Gustafsson, Audrey Y Chu, Karol Estrada, Jian'an Luan, Zoltan Kutalik, Najaf Amin, Martin L Buchkovich, Damien C Croteau-Chonka, Felix R Day, Yanan Duan, Tove Fall, Rudolf Fehrmann, Teresa Ferreira, Anne U Jackson, Juha Karjalainen, Ken Sin Lo, Adam E Locke, Reedik Mägi, Evelin Mihailov, Eleonora Porcu, Joshua C Randall, André Scherag, Anna A E Vinkhuyzen, Harm-Jan Westra, Thomas W Winkler, Tsegaselassie Workalemahu, Jing Hua Zhao, Devin Absher, Eva Albrecht, Denise Anderson, Jeffrey Baron, Marian Beekman, Ayse Demirkan, Georg B Ehret, Bjarke Feenstra, Mary F Feitosa, Krista Fischer, Ross M Fraser, Anuj Goel, Jian Gong, Anne E Justice, Stavroula Kanoni, Marcus E Kleber, Kati Kristiansson, Unhee Lim, Vaneet Lotay, Julian C Lui, Massimo Mangino, Irene Mateo Leach, Carolina Medina-Gomez, Michael A Nalls, Dale R Nyholt, Cameron D Palmer, Dorota Pasko, Sonali Pechlivanis, Inga Prokopenko, Janina S Ried, Stephan Ripke, Dmitry Shungin, Alena Stančáková, Rona J Strawbridge, Yun Ju Sung, Toshiko Tanaka, Alexander Teumer, Stella Trompet, Sander W van der Laan, Jessica van Setten, Jana V van Vliet-Ostaptchouk, Zhaoming Wang, Loïc Yengo, Weihua Zhang, Uzma Afzal, Johan Arnlöv, Gillian M Arscott, Stefania Bandinelli, Amy Barrett, Claire Bellis, Amanda J Bennett, Christian Berne, Matthias Blüher, Jennifer L Bolton, Yvonne Böttcher, Heather A Boyd, Marcel Bruinenberg, Brendan M Buckley, Steven Buyske, Ida H Caspersen, Peter S Chines, Robert Clarke, Simone Claudi-Boehm, Matthew Cooper, E Warwick Daw, Pim A de Jong, Joris Deelen, Graciela Delgado, Josh C Denny, Rosalie Dhonukshe-Rutten, Maria Dimitriou, Alex S F Doney, Marcus Dörr, Niina Eklund, Elodie Eury, Lasse Folkersen, Melissa E Garcia, Frank Geller, Vilmantas Giedraitis, Alan S Go, Harald Grallert, Tanja B Grammer, Jürgen Gräßler, Henrik Grönberg, Lisette C P G M de Groot, Christopher J Groves, Jeffrey Haessler, Per Hall, Toomas Haller, Göran Hallmans, Anke Hannemann, Catharina A Hartman, Maija Hassinen, Caroline Hayward, Nancy L Heard-Costa, Quinta Helmer, Gibran Hemani, Anjali K Henders, Hans L Hillege, Mark A Hlatky, Wolfgang Hoffmann, Per Hoffmann, Oddgeir Holmen, Jeanine J Houwing-Duistermaat, Thomas Illig, Aaron Isaacs, Alan L James, Janina Jeff, Berit Johansen, Asa Johansson, Jennifer Jolley, Thorhildur Juliusdottir, Juhani Junttila, Abel N Kho, Leena Kinnunen, Norman Klopp, Thomas Kocher, Wolfgang Kratzer, Peter Lichtner, Lars Lind, Jaana Lindström, Stéphane Lobbens, Mattias Lorentzon, Yingchang Lu, Valeriya Lyssenko, Patrik K E Magnusson, Anubha Mahajan, Marc Maillard, Wendy L McArdle, Colin A McKenzie, Stela McLachlan, Paul J McLaren, Cristina Menni, Sigrun Merger, Lili Milani, Alireza Moayyeri, Keri L Monda, Mario A Morken, Gabriele Müller, Martina Müller-Nurasyid, Arthur W Musk, Narisu Narisu, Matthias Nauck, Ilja M Nolte, Markus M Nöthen, Laticia Oozageer, Stefan Pilz, Nigel W Rayner, Frida Renstrom, Neil R Robertson, Lynda M Rose, Ronan Roussel, Serena Sanna, Hubert Scharnagl, Salome Scholtens, Fredrick R Schumacher, Heribert Schunkert, Robert A Scott, Joban Sehmi, Thomas Seufferlein, Jianxin Shi, Karri Silventoinen, Johannes H Smit, Albert Vernon Smith, Joanna Smolonska, Alice V Stanton, Kathleen Stirrups, David J Stott, Heather M Stringham, Johan Sundström, Morris A Swertz, Ann-Christine Syvänen, Bamidele O Tayo, Gudmar Thorleifsson, Jonathan P Tyrer, Suzanne van Dijk, Natasja M van Schoor, Nathalie van der Velde, Diana van Heemst, Floor V A van Oort, Sita H Vermeulen, Niek Verweij, Judith M Vonk, Lindsay L Waite, Melanie Waldenberger, Roman Wennauer, Lynne R Wilkens, Christina Willenborg, Tom Wilsgaard, Mary K Wojczynski, Andrew Wong, Alan F Wright, Qunyuan Zhang, Dominique Arveiler, Stephan J L Bakker, John Beilby, Richard N Bergman, Sven Bergmann, Reiner Biffar, John Blangero, Dorret I Boomsma, Stefan R Bornstein, Pascal Bovet, Paolo Brambilla, Morris J Brown, Harry Campbell, Mark J Caulfield, Aravinda Chakravarti, Rory Collins, Francis S Collins, Dana C Crawford, L Adrienne Cupples, John Danesh, Ulf de Faire, Hester M den Ruijter, Raimund Erbel, Jeanette Erdmann, Johan G Eriksson, Martin Farrall, Ele Ferrannini, Jean Ferrières, Ian Ford, Nita G Forouhi, Terrence Forrester, Ron T Gansevoort, Pablo V Gejman, Christian Gieger, Alain Golay, Omri Gottesman, Vilmundur Gudnason, Ulf Gyllensten, David W Haas, Alistair S Hall, Tamara B Harris, Andrew T Hattersley, Andrew C Heath, Christian Hengstenberg, Andrew A Hicks, Lucia A Hindorff, Aroon D Hingorani, Albert Hofman, G Kees Hovingh, Steve E Humphries, Steven C Hunt, Elina Hyppönen, Kevin B Jacobs, Marjo-Riitta Järvelin, Pekka Jousilahti, Antti M Jula, Jaakko Kaprio, John J P Kastelein, Manfred Kayser, Frank Kee, Sirkka M Keinanen-Kiukaanniemi, Lambertus A Kiemeney, Jaspal S Kooner, Charles Kooperberg, Seppo Koskinen, Peter Kovacs, Aldi T Kraja, Meena Kumari, Johanna Kuusisto, Timo A Lakka, Claudia Langenberg, Loic Le Marchand, Terho Lehtimäki, Sara Lupoli, Pamela A F Madden, Satu Mannisto, Paolo Manunta, André Marette, Tara C Matise, Barbara McKnight, Thomas Meitinger, Frans L Moll, Grant W Montgomery, Andrew D Morris, Andrew P Morris, Jeffrey C Murray, Mari Nelis, Claes Ohlsson, Albertine J Oldehinkel, Ken K Ong, Willem H Ouwehand, Gerard Pasterkamp, Annette Peters, Peter P Pramstaller, Jackie F Price, Lu Qi, Olli T Raitakari, Tuomo Rankinen, D C Rao, Treva K Rice, Marylyn Ritchie, Igor Rudan, Veikko Salomaa, Nilesh J Samani, Jouko Saramies, Mark A Sarzynski, Peter E H Schwarz, Sylvain Sebert, Peter Sever, Alan R Shuldiner, Juha Sinisalo, Valgerdur Steinthorsdottir, Ronald P Stolk, Jean-Claude Tardif, Anke Tönjes, Angelo Tremblay, Elena Tremoli, Jarmo Virtamo, Marie-Claude Vohl, , Philippe Amouyel, Folkert W Asselbergs, Themistocles L Assimes, Murielle Bochud, Bernhard O Boehm, Eric Boerwinkle, Erwin P Bottinger, Claude Bouchard, Stéphane Cauchi, John C Chambers, Stephen J Chanock, Richard S Cooper, Paul I W de Bakker, George Dedoussis, Luigi Ferrucci, Paul W Franks, Philippe Froguel, Leif C Groop, Christopher A Haiman, Anders Hamsten, M Geoffrey Hayes, Jennie Hui, David J Hunter, Kristian Hveem, J Wouter Jukema, Robert C Kaplan, Mika Kivimäki, Diana Kuh, Markku Laakso, Yongmei Liu, Nicholas G Martin, Winfried März, Mads Melbye, Susanne Moebus, Patricia B Munroe, Inger Njølstad, Ben A Oostra, Colin N A Palmer, Nancy L Pedersen, Markus Perola, Louis Pérusse, Ulrike Peters, Joseph E Powell, Chris Power, Thomas Quertermous, Rainer Rauramaa, Eva Reinmaa, Paul M Ridker, Fernando Rivadeneira, Jerome I Rotter, Timo E Saaristo, Danish Saleheen, David Schlessinger, P Eline Slagboom, Harold Snieder, Tim D Spector, Konstantin Strauch, Michael Stumvoll, Jaakko Tuomilehto, Matti Uusitupa, Pim van der Harst, Henry Völzke, Mark Walker, Nicholas J Wareham, Hugh Watkins, H-Erich Wichmann, James F Wilson, Pieter Zanen, Panos Deloukas, Iris M Heid, Cecilia M Lindgren, Karen L Mohlke, Elizabeth K Speliotes, Unnur Thorsteinsdottir, Inês Barroso, Caroline S Fox, Kari E North, David P Strachan, Jacques S Beckmann, Sonja I Berndt, Michael Boehnke, Ingrid B Borecki, Mark I McCarthy, Andres Metspalu, Kari Stefansson, André G Uitterlinden, Cornelia M van Duijn, Lude Franke, Cristen J Willer, Alkes L Price, Guillaume Lettre, Ruth J F Loos, Michael N Weedon, Erik Ingelsson, Jeffrey R O'Connell, Gonçalo R Abecasis, Daniel I Chasman, Michael E Goddard, Peter M Visscher, Joel N Hirschhorn, Timothy M Frayling.
Nat. Genet.
PUBLISHED: 08-29-2014
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Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ?2,000, ?3,700 and ?9,500 SNPs explained ?21%, ?24% and ?29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/?-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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The South Asian genome.
PLoS ONE
PUBLISHED: 08-12-2014
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The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.
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Genetic evidence for a normal-weight "metabolically obese" phenotype linking insulin resistance, hypertension, coronary artery disease, and type 2 diabetes.
Diabetes
PUBLISHED: 07-21-2014
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The mechanisms that predispose to hypertension, coronary artery disease (CAD), and type 2 diabetes (T2D) in individuals of normal weight are poorly understood. In contrast, in monogenic primary lipodystrophy-a reduction in subcutaneous adipose tissue-it is clear that it is adipose dysfunction that causes severe insulin resistance (IR), hypertension, CAD, and T2D. We aimed to test the hypothesis that common alleles associated with IR also influence the wider clinical and biochemical profile of monogenic IR. We selected 19 common genetic variants associated with fasting insulin-based measures of IR. We used hierarchical clustering and results from genome-wide association studies of eight nondisease outcomes of monogenic IR to group these variants. We analyzed genetic risk scores against disease outcomes, including 12,171 T2D cases, 40,365 CAD cases, and 69,828 individuals with blood pressure measurements. Hierarchical clustering identified 11 variants associated with a metabolic profile consistent with a common, subtle form of lipodystrophy. A genetic risk score consisting of these 11 IR risk alleles was associated with higher triglycerides (? = 0.018; P = 4 × 10(-29)), lower HDL cholesterol (? = -0.020; P = 7 × 10(-37)), greater hepatic steatosis (? = 0.021; P = 3 × 10(-4)), higher alanine transaminase (? = 0.002; P = 3 × 10(-5)), lower sex-hormone-binding globulin (? = -0.010; P = 9 × 10(-13)), and lower adiponectin (? = -0.015; P = 2 × 10(-26)). The same risk alleles were associated with lower BMI (per-allele ? = -0.008; P = 7 × 10(-8)) and increased visceral-to-subcutaneous adipose tissue ratio (? = -0.015; P = 6 × 10(-7)). Individuals carrying ?17 fasting insulin-raising alleles (5.5% population) were slimmer (0.30 kg/m(2)) but at increased risk of T2D (odds ratio [OR] 1.46; per-allele P = 5 × 10(-13)), CAD (OR 1.12; per-allele P = 1 × 10(-5)), and increased blood pressure (systolic and diastolic blood pressure of 1.21 mmHg [per-allele P = 2 × 10(-5)] and 0.67 mmHg [per-allele P = 2 × 10(-4)], respectively) compared with individuals carrying ?9 risk alleles (5.5% population). Our results provide genetic evidence for a link between the three diseases of the "metabolic syndrome" and point to reduced subcutaneous adiposity as a central mechanism.
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Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.
PLoS Genet.
PUBLISHED: 07-01-2014
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The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ?4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta?=?0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.
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Critical cultural awareness: contributions to a globalizing psychology.
Am Psychol
PUBLISHED: 05-19-2014
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The number of psychologists whose work crosses cultural boundaries is increasing. Without a critical awareness of their own cultural grounding, they risk imposing the assumptions, concepts, practices, and values of U.S.-centered psychology on societies where they do not fit, as a brief example from the 2004 Indian Ocean tsunami shows. Hermeneutic thinkers offer theoretical resources for gaining cultural awareness. Culture, in the hermeneutic view, is the constellation of meanings that constitutes a way of life. Such cultural meanings-especially in the form of folk psychologies and moral visions-inevitably shape every psychology, including U.S. psychology. The insights of hermeneutics, as well as its conceptual resources and research approaches, open the way for psychological knowledge and practice that are more culturally situated.
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Clopidogrel as prophylactic treatment for migraine: A pilot randomised, controlled study.
Cephalalgia
PUBLISHED: 05-16-2014
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Anecdotal reports suggest that clopidogrel may prevent migraine attacks. We undertook a pilot randomised trial.
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Adjusting parameters of aortic valve stenosis severity by body size.
Heart
PUBLISHED: 04-29-2014
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Adjustment of cardiac dimensions by measures of body size appears intuitively convincing and in patients with aortic stenosis, aortic valve area (AVA) is commonly adjusted by body surface area (BSA). However, there is little evidence to support such an approach.
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A prospective study of the impact of serial troponin measurements on the diagnosis of myocardial infarction and hospital and six-month mortality in patients admitted to ICU with non-cardiac diagnoses.
Crit Care
PUBLISHED: 03-27-2014
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Troponin T (cTnT) elevation is common in patients in the Intensive Care Unit (ICU) and associated with morbidity and mortality. Our aim was to determine the epidemiology of raised cTnT levels and contemporaneous electrocardiogram (ECG) changes suggesting myocardial infarction (MI) in ICU patients admitted for non-cardiac reasons.
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Detection of heart disease by open access echocardiography: a retrospective analysis of general practice referrals.
Br J Gen Pract
PUBLISHED: 02-26-2014
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Heart disease is difficult to detect clinically and it has been suggested that echocardiography should be available to all patients with possible cardiac symptoms or signs.
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Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.
Nat. Genet.
PUBLISHED: 02-10-2014
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Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.
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Echocardiography predicts major adverse cardiovascular events after renal transplantation.
Nephron Clin Pract
PUBLISHED: 01-20-2014
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Cardiovascular disease is a leading cause of morbidity and mortality after renal transplantation. We analysed whether pre-transplant transthoracic echocardiograms (TTE) predicted major adverse cardiovascular events (MACE) after transplant.
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Associations of genetic variants in/near body mass index-associated genes with type 2 diabetes: a systematic meta-analysis.
Clin. Endocrinol. (Oxf)
PUBLISHED: 01-12-2014
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Genome-wide association studies have identified many obesity/body mass index (BMI)-associated loci in Europeans and East Asians. Since then, a large number of studies have investigated the role of BMI-associated loci in the development of type 2 diabetes (T2D). However, the results have been inconsistent. The objective of this study was to investigate the associations of eleven obesity/BMI loci with T2D risk and explore how BMI influences this risk.
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Multimodality imaging of heart valve disease.
Arq. Bras. Cardiol.
PUBLISHED: 01-07-2014
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Unidentified heart valve disease is associated with a significant morbidity and mortality. It has therefore become important to accurately identify, assess and monitor patients with this condition in order that appropriate and timely intervention can occur. Although echocardiography has emerged as the predominant imaging modality for this purpose, recent advances in cardiac magnetic resonance and cardiac computed tomography indicate that they may have an important contribution to make. The current review describes the assessment of regurgitant and stenotic heart valves by multimodality imaging (echocardiography, cardiac computed tomography and cardiac magnetic resonance) and discusses their relative strengths and weaknesses.
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Coronary heart disease in Indian Asians.
Glob Cardiol Sci Pract
PUBLISHED: 01-01-2014
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The Indian Asian population accounts for a fifth of all global deaths from coronary heart disease (CHD). CHD deaths on the Indian subcontinent have doubled since 1990, and are predicted to rise a further 50% by 2030. Reasons underlying the increased CHD mortality among Indian Asians remain unknown. Although conventional cardiovascular risk factors contribute to CHD in Indian Asians as in other populations, these do not account for their increased risk. Type-2 diabetes, insulin resistance and related metabolic disturbances are more prevalent amongst Indian Asians than Europeans, and have been proposed as major determinants of higher CHD risk among Indian Asians. However, this view is not supported by prospective data. Genome-wide association studies have not identified differences in allele frequencies or effect sizes in known loci to explain the increased CHD risk in Indian Asians. Limited knowledge of mechanisms underlying higher CHD risk amongst Indian Asians presents a major obstacle to reducing the burden of CHD in this population. Systems biology approaches such as genomics, epigenomics, metabolomics and transcriptomics, provide a non-biased approach for discovery of novel biomarkers and disease pathways underlying CHD. Incorporation of these 'omic' approaches in prospective Indian Asian cohorts such as the London Life Sciences Population Study (LOLIPOP) provide an exciting opportunity for the identification of new risk factors underlying CHD in this high risk population.
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Better Off Than We Know: Distorted Perceptions of Incomes and Income Inequality in America.
Psychol Sci
PUBLISHED: 12-06-2013
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Three studies examined Americans perceptions of incomes and income inequality using a variety of criterion measures. Contrary to recent findings indicating that Americans underestimate wealth inequality, we found that Americans not only overestimated the rise of income inequality over time, but also underestimated average incomes. Thus, economic conditions in America are more favorable than people seem to realize. Furthermore, ideological differences emerged in two of these studies, such that political liberals overestimated the rise of inequality more than political conservatives. Implications of these findings for public policy debates and ideological disagreements are discussed.
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Ethnicity differences in genetic susceptibility to ulcerative colitis: a comparison of Indian asians and white northern Europeans.
Inflamm. Bowel Dis.
PUBLISHED: 10-23-2013
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Studies in Caucasian populations have identified a number of genetic associations with ulcerative colitis (UC), but reports from other ethnic groups have been limited. Recent studies from India have reported an association with UC and a single polymorphism (SNP) in CARD15/NOD2 (SNP5, rs2066842), which has not been reported in Caucasian UC cohorts. In addition, strong genetic associations with SNPs in the HLA region have been reported in Indian UC populations. However, there have been no reports on the frequency of HLA class II alleles in Indian populations with inflammatory bowel disease to examine whether the associations differ from other ethnic populations.
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Discovery and refinement of loci associated with lipid levels.
, Cristen J Willer, Ellen M Schmidt, Sebanti Sengupta, Gina M Peloso, Stefan Gustafsson, Stavroula Kanoni, Andrea Ganna, Jin Chen, Martin L Buchkovich, Samia Mora, Jacques S Beckmann, Jennifer L Bragg-Gresham, Hsing-Yi Chang, Ayse Demirkan, Heleen M den Hertog, Ron Do, Louise A Donnelly, Georg B Ehret, Tonu Esko, Mary F Feitosa, Teresa Ferreira, Krista Fischer, Pierre Fontanillas, Ross M Fraser, Daniel F Freitag, Deepti Gurdasani, Kauko Heikkilä, Elina Hyppönen, Aaron Isaacs, Anne U Jackson, Asa Johansson, Toby Johnson, Marika Kaakinen, Johannes Kettunen, Marcus E Kleber, Xiaohui Li, Jian'an Luan, Leo-Pekka Lyytikäinen, Patrik K E Magnusson, Massimo Mangino, Evelin Mihailov, May E Montasser, Martina Müller-Nurasyid, Ilja M Nolte, Jeffrey R O'Connell, Cameron D Palmer, Markus Perola, Ann-Kristin Petersen, Serena Sanna, Richa Saxena, Susan K Service, Sonia Shah, Dmitry Shungin, Carlo Sidore, Ci Song, Rona J Strawbridge, Ida Surakka, Toshiko Tanaka, Tanya M Teslovich, Gudmar Thorleifsson, Evita G van den Herik, Benjamin F Voight, Kelly A Volcik, Lindsay L Waite, Andrew Wong, Ying Wu, Weihua Zhang, Devin Absher, Gershim Asiki, Inês Barroso, Latonya F Been, Jennifer L Bolton, Lori L Bonnycastle, Paolo Brambilla, Mary S Burnett, Giancarlo Cesana, Maria Dimitriou, Alex S F Doney, Angela Döring, Paul Elliott, Stephen E Epstein, Gudmundur Ingi Eyjolfsson, Bruna Gigante, Mark O Goodarzi, Harald Grallert, Martha L Gravito, Christopher J Groves, Göran Hallmans, Anna-Liisa Hartikainen, Caroline Hayward, Dena Hernandez, Andrew A Hicks, Hilma Holm, Yi-Jen Hung, Thomas Illig, Michelle R Jones, Pontiano Kaleebu, John J P Kastelein, Kay-Tee Khaw, Eric Kim, Norman Klopp, Pirjo Komulainen, Meena Kumari, Claudia Langenberg, Terho Lehtimäki, Shih-Yi Lin, Jaana Lindström, Ruth J F Loos, François Mach, Wendy L McArdle, Christa Meisinger, Braxton D Mitchell, Gabrielle Müller, Ramaiah Nagaraja, Narisu Narisu, Tuomo V M Nieminen, Rebecca N Nsubuga, Isleifur Olafsson, Ken K Ong, Aarno Palotie, Theodore Papamarkou, Cristina Pomilla, Anneli Pouta, Daniel J Rader, Muredach P Reilly, Paul M Ridker, Fernando Rivadeneira, Igor Rudan, Aimo Ruokonen, Nilesh Samani, Hubert Scharnagl, Janet Seeley, Kaisa Silander, Alena Stančáková, Kathleen Stirrups, Amy J Swift, Laurence Tiret, André G Uitterlinden, L Joost van Pelt, Sailaja Vedantam, Nicholas Wainwright, Cisca Wijmenga, Sarah H Wild, Gonneke Willemsen, Tom Wilsgaard, James F Wilson, Elizabeth H Young, Jing Hua Zhao, Linda S Adair, Dominique Arveiler, Themistocles L Assimes, Stefania Bandinelli, Franklyn Bennett, Murielle Bochud, Bernhard O Boehm, Dorret I Boomsma, Ingrid B Borecki, Stefan R Bornstein, Pascal Bovet, Michel Burnier, Harry Campbell, Aravinda Chakravarti, John C Chambers, Yii-Der Ida Chen, Francis S Collins, Richard S Cooper, John Danesh, George Dedoussis, Ulf de Faire, Alan B Feranil, Jean Ferrières, Luigi Ferrucci, Nelson B Freimer, Christian Gieger, Leif C Groop, Vilmundur Gudnason, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Aroon Hingorani, Joel N Hirschhorn, Albert Hofman, G Kees Hovingh, Chao Agnes Hsiung, Steve E Humphries, Steven C Hunt, Kristian Hveem, Carlos Iribarren, Marjo-Riitta Järvelin, Antti Jula, Mika Kähönen, Jaakko Kaprio, Antero Kesäniemi, Mika Kivimäki, Jaspal S Kooner, Peter J Koudstaal, Ronald M Krauss, Diana Kuh, Johanna Kuusisto, Kirsten O Kyvik, Markku Laakso, Timo A Lakka, Lars Lind, Cecilia M Lindgren, Nicholas G Martin, Winfried März, Mark I McCarthy, Colin A McKenzie, Pierre Meneton, Andres Metspalu, Leena Moilanen, Andrew D Morris, Patricia B Munroe, Inger Njølstad, Nancy L Pedersen, Chris Power, Peter P Pramstaller, Jackie F Price, Bruce M Psaty, Thomas Quertermous, Rainer Rauramaa, Danish Saleheen, Veikko Salomaa, Dharambir K Sanghera, Jouko Saramies, Peter E H Schwarz, Wayne H-H Sheu, Alan R Shuldiner, Agneta Siegbahn, Tim D Spector, Kari Stefansson, David P Strachan, Bamidele O Tayo, Elena Tremoli, Jaakko Tuomilehto, Matti Uusitupa, Cornelia M van Duijn, Peter Vollenweider, Lars Wallentin, Nicholas J Wareham, John B Whitfield, Bruce H R Wolffenbuttel, José M Ordovás, Eric Boerwinkle, Colin N A Palmer, Unnur Thorsteinsdottir, Daniel I Chasman, Jerome I Rotter, Paul W Franks, Samuli Ripatti, L Adrienne Cupples, Manjinder S Sandhu, Stephen S Rich, Michael Boehnke, Panos Deloukas, Sekar Kathiresan, Karen L Mohlke, Erik Ingelsson, Gonçalo R Abecasis.
Nat. Genet.
PUBLISHED: 09-13-2013
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Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.
Conall M O'Seaghdha, Hongsheng Wu, Qiong Yang, Karen Kapur, Idris Guessous, Annie Mercier Zuber, Anna Köttgen, Candice Stoudmann, Alexander Teumer, Zoltan Kutalik, Massimo Mangino, Abbas Dehghan, Weihua Zhang, Gudny Eiriksdottir, Guo Li, Toshiko Tanaka, Laura Portas, Lorna M Lopez, Caroline Hayward, Kurt Lohman, Koichi Matsuda, Sandosh Padmanabhan, Dmitri Firsov, Rossella Sorice, Sheila Ulivi, A Catharina Brockhaus, Marcus E Kleber, Anubha Mahajan, Florian D Ernst, Vilmundur Gudnason, Lenore J Launer, Aurelien Macé, Eric Boerwinckle, Dan E Arking, Chizu Tanikawa, Yusuke Nakamura, Morris J Brown, Jean-Michel Gaspoz, Jean-Marc Theler, David S Siscovick, Bruce M Psaty, Sven Bergmann, Peter Vollenweider, Veronique Vitart, Alan F Wright, Tatijana Zemunik, Mladen Boban, Ivana Kolčić, Pau Navarro, Edward M Brown, Karol Estrada, Jingzhong Ding, Tamara B Harris, Stefania Bandinelli, Dena Hernandez, Andrew B Singleton, Giorgia Girotto, Daniela Ruggiero, Adamo Pio D'adamo, Antonietta Robino, Thomas Meitinger, Christa Meisinger, Gail Davies, John M Starr, John C Chambers, Bernhard O Boehm, Bernhard R Winkelmann, Jie Huang, Federico Murgia, Sarah H Wild, Harry Campbell, Andrew P Morris, Oscar H Franco, Albert Hofman, André G Uitterlinden, Fernando Rivadeneira, Uwe Völker, Anke Hannemann, Reiner Biffar, Wolfgang Hoffmann, So-Youn Shin, Pierre Lescuyer, Hughes Henry, Claudia Schurmann, , Patricia B Munroe, Paolo Gasparini, Nicola Pirastu, Marina Ciullo, Christian Gieger, Winfried März, Lars Lind, Tim D Spector, Albert V Smith, Igor Rudan, James F Wilson, Ozren Polašek, Ian J Deary, Mario Pirastu, Luigi Ferrucci, Yongmei Liu, Bryan Kestenbaum, Jaspal S Kooner, Jacqueline C M Witteman, Matthias Nauck, W H Linda Kao, Henri Wallaschofski, Olivier Bonny, Caroline S Fox, Murielle Bochud.
PLoS Genet.
PUBLISHED: 09-01-2013
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Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ? 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.
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Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.
Maria Sabater-Lleal, Jie Huang, Daniel Chasman, Silvia Naitza, Abbas Dehghan, Andrew D Johnson, Alexander Teumer, Alex P Reiner, Lasse Folkersen, Saonli Basu, Alicja R Rudnicka, Stella Trompet, Anders Malarstig, Jens Baumert, Joshua C Bis, Xiuqing Guo, Jouke J Hottenga, So-Youn Shin, Lorna M Lopez, Jari Lahti, Toshiko Tanaka, Lisa R Yanek, Tiphaine Oudot-Mellakh, James F Wilson, Pau Navarro, Jennifer E Huffman, Tatijana Zemunik, Susan Redline, Reena Mehra, Drazen Pulanić, Igor Rudan, Alan F Wright, Ivana Kolčić, Ozren Polašek, Sarah H Wild, Harry Campbell, J David Curb, Robert Wallace, Simin Liu, Charles B Eaton, Diane M Becker, Lewis C Becker, Stefania Bandinelli, Katri Räikkönen, Elisabeth Widén, Aarno Palotie, Myriam Fornage, David Green, Myron Gross, Gail Davies, Sarah E Harris, David C Liewald, John M Starr, Frances M K Williams, Peter J Grant, Timothy D Spector, Rona J Strawbridge, Angela Silveira, Bengt Sennblad, Fernando Rivadeneira, André G Uitterlinden, Oscar H Franco, Albert Hofman, Jenny van Dongen, Gonneke Willemsen, Dorret I Boomsma, Jie Yao, Nancy Swords Jenny, Talin Haritunians, Barbara McKnight, Thomas Lumley, Kent D Taylor, Jerome I Rotter, Bruce M Psaty, Annette Peters, Christian Gieger, Thomas Illig, Anne Grotevendt, Georg Homuth, Henry Völzke, Thomas Kocher, Anuj Goel, Maria Grazia Franzosi, Udo Seedorf, Robert Clarke, Maristella Steri, Kirill V Tarasov, Serena Sanna, David Schlessinger, David J Stott, Naveed Sattar, Brendan M Buckley, Ann Rumley, Gordon D Lowe, Wendy L McArdle, Ming-Huei Chen, Geoffrey H Tofler, Jaejoon Song, Eric Boerwinkle, Aaron R Folsom, Lynda M Rose, Anders Franco-Cereceda, Martina Teichert, M Arfan Ikram, Thomas H Mosley, Steve Bevan, Martin Dichgans, Peter M Rothwell, Cathie L M Sudlow, Jemma C Hopewell, John C Chambers, Danish Saleheen, Jaspal S Kooner, John Danesh, Christopher P Nelson, Jeanette Erdmann, Muredach P Reilly, Sekar Kathiresan, Heribert Schunkert, Pierre-Emmanuel Morange, Luigi Ferrucci, Johan G Eriksson, David Jacobs, Ian J Deary, Nicole Soranzo, Jacqueline C M Witteman, Eco J C de Geus, Russell P Tracy, Caroline Hayward, Wolfgang Koenig, Francesco Cucca, J Wouter Jukema, Per Eriksson, Sudha Seshadri, Hugh S Markus, Hugh Watkins, Nilesh J Samani, , Henri Wallaschofski, Nicholas L Smith, David Tregouet, Paul M Ridker, Weihong Tang, David P Strachan, Anders Hamsten, Christopher J O'Donnell.
Circulation
PUBLISHED: 08-22-2013
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Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation.
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Indexing aortic valve area by body surface area increases the prevalence of severe aortic stenosis.
Heart
PUBLISHED: 08-22-2013
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To account for differences in body size in patients with aortic stenosis, aortic valve area (AVA) is divided by body surface area (BSA) to calculate indexed AVA (AVAindex). Cut-off values for severe stenosis are <1.0 cm(2) for AVA and <0.6 cm(2)/m(2) for AVAindex.
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Virtual fractional flow reserve by coronary computed tomography - hope or hype?
EuroIntervention
PUBLISHED: 06-25-2013
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Studies evaluating the diagnostic performance of coronary computed tomography angiography (CTA) are consistent in demonstrating a high negative predictive accuracy, but only a modest positive predictive accuracy for the detection of significant coronary artery disease. Consequentially, there has been a considerable effort made to enhance the diagnostic capability of coronary CTA by developing scanner technology and also post-processing algorithms for coronary stenosis evaluation. Of these new developments, the proposition of being able to measure non-invasive fractional flow reserve by coronary computed tomography angiography (FFRct) has generated much recent interest. Initial reports indicate that the application FFRct not only correlates well with invasive fractional flow reserve but also has the potential to enhance substantially the positive predictive accuracy and overall accuracy of coronary CTA. Although it is theoretically possible to measure FFRct using complex computational fluid dynamics adapted from the aeronautical industry, this approach is likely to face a number of challenges prior to it being accepted into the mainstream as an adjunct to coronary CTA. The aim of the current review is to provide an overview of: 1) the fundamental engineering principles behind computational fluid dynamic modelling of coronary arterial blood flow; 2) the difficulties faced from an engineering perspective in developing a truly representative model; and 3) the challenges this technology is likely to face as it attempts to enter the clinical domain.
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Guidelines in cardiac clinical practice: evaluation of their methodological quality using the AGREE II instrument.
J R Soc Med
PUBLISHED: 05-28-2013
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Although clinical guidelines have an influential role in healthcare practice, their development process and the evidence they cite has been subject to criticism. This study evaluates the quality of guidelines in cardiac clinical practice by examining how they adhere to validated methodological standards in guideline development. A structured review of cardiac clinical practice guidelines published in seven cardiovascular journals between January 2001 and May 2011 was performed. The AGREE II assessment tool was used by two researchers to evaluate guideline quality. A total of 101 guidelines were identified. Assessment of guidelines using AGREE II found methodological quality to be highly variable (median score, 58.70%; range, 45.34-76.40%). Scope and purpose (median score, 86.1%) and clarity of development (median score, 83.3 %) were the two domains within AGREE II that received the highest scores. Applicability (median score, 20.80%; range, 4.20-54.20%) and editorial independence (median score, 33.30%; range, 0-62.50%) had the lowest scores. There is considerable variability in the quality of cardiac clinical practice guidelines and this has not improved over the last 10 years. Incorporating validated guideline assessment tools, such as AGREE II, may improve the quality of guidelines.
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A training programme in screening echocardiography.
Clin Teach
PUBLISHED: 05-10-2013
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? Although the value of echocardiography in acutely unwell patients is well established, it is often difficult to deliver conventional studies immediately. This has led to the development of training programmes in screening echocardiography.
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Association of migraine aura with patent foramen ovale and atrial septal aneurysms.
Int. J. Cardiol.
PUBLISHED: 04-27-2013
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The relationship between migrainous aura and patent foramen ovale (PFO) remains uncertain
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Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci.
Genome Res.
PUBLISHED: 04-09-2013
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Nearly three-quarters of the 143 genetic signals associated with platelet and erythrocyte phenotypes identified by meta-analyses of genome-wide association (GWA) studies are located at non-protein-coding regions. Here, we assessed the role of candidate regulatory variants associated with cell type-restricted, closely related hematological quantitative traits in biologically relevant hematopoietic cell types. We used formaldehyde-assisted isolation of regulatory elements followed by next-generation sequencing (FAIRE-seq) to map regions of open chromatin in three primary human blood cells of the myeloid lineage. In the precursors of platelets and erythrocytes, as well as in monocytes, we found that open chromatin signatures reflect the corresponding hematopoietic lineages of the studied cell types and associate with the cell type-specific gene expression patterns. Dependent on their signal strength, open chromatin regions showed correlation with promoter and enhancer histone marks, distance to the transcription start site, and ontology classes of nearby genes. Cell type-restricted regions of open chromatin were enriched in sequence variants associated with hematological indices. The majority (63.6%) of such candidate functional variants at platelet quantitative trait loci (QTLs) coincided with binding sites of five transcription factors key in regulating megakaryopoiesis. We experimentally tested 13 candidate regulatory variants at 10 platelet QTLs and found that 10 (76.9%) affected protein binding, suggesting that this is a frequent mechanism by which regulatory variants influence quantitative trait levels. Our findings demonstrate that combining large-scale GWA data with open chromatin profiles of relevant cell types can be a powerful means of dissecting the genetic architecture of closely related quantitative traits.
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Effect of overweight and obesity on cardiovascular events in asymptomatic aortic stenosis: a SEAS substudy (Simvastatin Ezetimibe in Aortic Stenosis).
J. Am. Coll. Cardiol.
PUBLISHED: 03-26-2013
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This study investigated whether overweight and obesity impacted outcome in patients with aortic valve stenosis (AS).
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Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
Marcel den Hoed, Mark Eijgelsheim, Tonu Esko, Bianca J J M Brundel, David S Peal, David M Evans, Ilja M Nolte, Ayellet V Segrè, Hilma Holm, Robert E Handsaker, Harm-Jan Westra, Toby Johnson, Aaron Isaacs, Jian Yang, Alicia Lundby, Jing Hua Zhao, Young Jin Kim, Min Jin Go, Peter Almgren, Murielle Bochud, Gabrielle Boucher, Marilyn C Cornelis, Daniel Gudbjartsson, David Hadley, Pim van der Harst, Caroline Hayward, Martin den Heijer, Wilmar Igl, Anne U Jackson, Zoltan Kutalik, Jian'an Luan, John P Kemp, Kati Kristiansson, Claes Ladenvall, Mattias Lorentzon, May E Montasser, Omer T Njajou, Paul F O'Reilly, Sandosh Padmanabhan, Beate St Pourcain, Tuomo Rankinen, Perttu Salo, Toshiko Tanaka, Nicholas J Timpson, Veronique Vitart, Lindsay Waite, William Wheeler, Weihua Zhang, Harmen H M Draisma, Mary F Feitosa, Kathleen F Kerr, Penelope A Lind, Evelin Mihailov, N Charlotte Onland-Moret, Ci Song, Michael N Weedon, Weijia Xie, Loïc Yengo, Devin Absher, Christine M Albert, Alvaro Alonso, Dan E Arking, Paul I W de Bakker, Beverley Balkau, Cristina Barlassina, Paola Benaglio, Joshua C Bis, Nabila Bouatia-Naji, Søren Brage, Stephen J Chanock, Peter S Chines, Mina Chung, Dawood Darbar, Christian Dina, Marcus Dörr, Paul Elliott, Stephan B Felix, Krista Fischer, Christian Fuchsberger, Eco J C de Geus, Philippe Goyette, Vilmundur Gudnason, Tamara B Harris, Anna-Liisa Hartikainen, Aki S Havulinna, Susan R Heckbert, Andrew A Hicks, Albert Hofman, Suzanne Holewijn, Femke Hoogstra-Berends, Jouke-Jan Hottenga, Majken K Jensen, Asa Johansson, Juhani Junttila, Stefan Kääb, Bart Kanon, Shamika Ketkar, Kay-Tee Khaw, Joshua W Knowles, Angrad S Kooner, Jan A Kors, Meena Kumari, Lili Milani, Päivi Laiho, Edward G Lakatta, Claudia Langenberg, Maarten Leusink, Yongmei Liu, Robert N Luben, Kathryn L Lunetta, Stacey N Lynch, Marcello R P Markus, Pedro Marques-Vidal, Irene Mateo Leach, Wendy L McArdle, Steven A McCarroll, Sarah E Medland, Kathryn A Miller, Grant W Montgomery, Alanna C Morrison, Martina Müller-Nurasyid, Pau Navarro, Mari Nelis, Jeffrey R O'Connell, Christopher J O'Donnell, Ken K Ong, Anne B Newman, Annette Peters, Ozren Polašek, Anneli Pouta, Peter P Pramstaller, Bruce M Psaty, Dabeeru C Rao, Susan M Ring, Elizabeth J Rossin, Diana Rudan, Serena Sanna, Robert A Scott, Jaban S Sehmi, Stephen Sharp, Jordan T Shin, Andrew B Singleton, Albert V Smith, Nicole Soranzo, Tim D Spector, Chip Stewart, Heather M Stringham, Kirill V Tarasov, André G Uitterlinden, Liesbeth Vandenput, Shih-Jen Hwang, John B Whitfield, Cisca Wijmenga, Sarah H Wild, Gonneke Willemsen, James F Wilson, Jacqueline C M Witteman, Andrew Wong, Quenna Wong, Yalda Jamshidi, Paavo Zitting, Jolanda M A Boer, Dorret I Boomsma, Ingrid B Borecki, Cornelia M van Duijn, Ulf Ekelund, Nita G Forouhi, Philippe Froguel, Aroon Hingorani, Erik Ingelsson, Mika Kivimäki, Richard A Kronmal, Diana Kuh, Lars Lind, Nicholas G Martin, Ben A Oostra, Nancy L Pedersen, Thomas Quertermous, Jerome I Rotter, Yvonne T van der Schouw, W M Monique Verschuren, Mark Walker, Demetrius Albanes, David O Arnar, Themistocles L Assimes, Stefania Bandinelli, Michael Boehnke, Rudolf A de Boer, Claude Bouchard, W L Mark Caulfield, John C Chambers, Gary Curhan, Daniele Cusi, Johan Eriksson, Luigi Ferrucci, Wiek H van Gilst, Nicola Glorioso, Jacqueline de Graaf, Leif Groop, Ulf Gyllensten, Wen-Chi Hsueh, Frank B Hu, Heikki V Huikuri, David J Hunter, Carlos Iribarren, Bo Isomaa, Marjo-Riitta Järvelin, Antti Jula, Mika Kähönen, Lambertus A Kiemeney, Melanie M van der Klauw, Jaspal S Kooner, Peter Kraft, Licia Iacoviello, Terho Lehtimäki, Marja-Liisa L Lokki, Braxton D Mitchell, Gerjan Navis, Markku S Nieminen, Claes Ohlsson, Neil R Poulter, Lu Qi, Olli T Raitakari, Eric B Rimm, John D Rioux, Federica Rizzi, Igor Rudan, Veikko Salomaa, Peter S Sever, Denis C Shields, Alan R Shuldiner, Juha Sinisalo, Alice V Stanton, Ronald P Stolk, David P Strachan, Jean-Claude Tardif, Unnur Thorsteinsdottir, Jaako Tuomilehto, Dirk J van Veldhuisen, Jarmo Virtamo, Jorma Viikari, Peter Vollenweider, Gérard Waeber, Elisabeth Widén, Yoon Shin Cho, Jesper V Olsen, Peter M Visscher, Cristen Willer, Lude Franke, , Jeanette Erdmann, John R Thompson, Arne Pfeufer, Nona Sotoodehnia, Christopher Newton-Cheh, Patrick T Ellinor, Bruno H Ch Stricker, Andres Metspalu, Markus Perola, Jacques S Beckmann, George Davey Smith, Kari Stefansson, Nicholas J Wareham, Patricia B Munroe, Ody C M Sibon, David J Milan, Harold Snieder, Nilesh J Samani, Ruth J F Loos.
Nat. Genet.
PUBLISHED: 03-21-2013
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Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.
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An insight into transcatheter aortic valve implantation-a perspective from multidetector-computed tomography.
Catheter Cardiovasc Interv
PUBLISHED: 03-18-2013
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Transcatheter aortic valve implantation (TAVI) has now become an acceptable alternative to surgical aortic valve replacement for patients with severe aortic stenosis at high risk. The early enthusiasm for this technology has not diminished but rather has developed at an unprecedented rate over the last decade. Alongside the developments in implantation technique, transcatheter design, and postprocedural care, cardiac imaging modalities have also had to concurrently evolve to meet the perpetual demand for lower peri- and postprocedural complication rates. Although transthoracic and transesophageal echocardiography remain vital in patients selection and periprocedural guidance, there is now emerging evidence that indicates that multidetector-computed tomography (MDCT) may also have an equally important role to play. The aim of the current review is to examine the modern role of MDCT in assessing patients with aortic stenosis being considered for TAVI. © 2012 Wiley Periodicals, Inc.
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Common variants associated with plasma triglycerides and risk for coronary artery disease.
Ron Do, Cristen J Willer, Ellen M Schmidt, Sebanti Sengupta, Chi Gao, Gina M Peloso, Stefan Gustafsson, Stavroula Kanoni, Andrea Ganna, Jin Chen, Martin L Buchkovich, Samia Mora, Jacques S Beckmann, Jennifer L Bragg-Gresham, Hsing-Yi Chang, Ayse Demirkan, Heleen M den Hertog, Louise A Donnelly, Georg B Ehret, Tonu Esko, Mary F Feitosa, Teresa Ferreira, Krista Fischer, Pierre Fontanillas, Ross M Fraser, Daniel F Freitag, Deepti Gurdasani, Kauko Heikkilä, Elina Hyppönen, Aaron Isaacs, Anne U Jackson, Asa Johansson, Toby Johnson, Marika Kaakinen, Johannes Kettunen, Marcus E Kleber, Xiaohui Li, Jian'an Luan, Leo-Pekka Lyytikäinen, Patrik K E Magnusson, Massimo Mangino, Evelin Mihailov, May E Montasser, Martina Müller-Nurasyid, Ilja M Nolte, Jeffrey R O'Connell, Cameron D Palmer, Markus Perola, Ann-Kristin Petersen, Serena Sanna, Richa Saxena, Susan K Service, Sonia Shah, Dmitry Shungin, Carlo Sidore, Ci Song, Rona J Strawbridge, Ida Surakka, Toshiko Tanaka, Tanya M Teslovich, Gudmar Thorleifsson, Evita G van den Herik, Benjamin F Voight, Kelly A Volcik, Lindsay L Waite, Andrew Wong, Ying Wu, Weihua Zhang, Devin Absher, Gershim Asiki, Inês Barroso, Latonya F Been, Jennifer L Bolton, Lori L Bonnycastle, Paolo Brambilla, Mary S Burnett, Giancarlo Cesana, Maria Dimitriou, Alex S F Doney, Angela Döring, Paul Elliott, Stephen E Epstein, Gudmundur Ingi Eyjolfsson, Bruna Gigante, Mark O Goodarzi, Harald Grallert, Martha L Gravito, Christopher J Groves, Göran Hallmans, Anna-Liisa Hartikainen, Caroline Hayward, Dena Hernandez, Andrew A Hicks, Hilma Holm, Yi-Jen Hung, Thomas Illig, Michelle R Jones, Pontiano Kaleebu, John J P Kastelein, Kay-Tee Khaw, Eric Kim, Norman Klopp, Pirjo Komulainen, Meena Kumari, Claudia Langenberg, Terho Lehtimäki, Shih-Yi Lin, Jaana Lindström, Ruth J F Loos, François Mach, Wendy L McArdle, Christa Meisinger, Braxton D Mitchell, Gabrielle Müller, Ramaiah Nagaraja, Narisu Narisu, Tuomo V M Nieminen, Rebecca N Nsubuga, Isleifur Olafsson, Ken K Ong, Aarno Palotie, Theodore Papamarkou, Cristina Pomilla, Anneli Pouta, Daniel J Rader, Muredach P Reilly, Paul M Ridker, Fernando Rivadeneira, Igor Rudan, Aimo Ruokonen, Nilesh Samani, Hubert Scharnagl, Janet Seeley, Kaisa Silander, Alena Stančáková, Kathleen Stirrups, Amy J Swift, Laurence Tiret, André G Uitterlinden, L Joost van Pelt, Sailaja Vedantam, Nicholas Wainwright, Cisca Wijmenga, Sarah H Wild, Gonneke Willemsen, Tom Wilsgaard, James F Wilson, Elizabeth H Young, Jing Hua Zhao, Linda S Adair, Dominique Arveiler, Themistocles L Assimes, Stefania Bandinelli, Franklyn Bennett, Murielle Bochud, Bernhard O Boehm, Dorret I Boomsma, Ingrid B Borecki, Stefan R Bornstein, Pascal Bovet, Michel Burnier, Harry Campbell, Aravinda Chakravarti, John C Chambers, Yii-Der Ida Chen, Francis S Collins, Richard S Cooper, John Danesh, George Dedoussis, Ulf de Faire, Alan B Feranil, Jean Ferrières, Luigi Ferrucci, Nelson B Freimer, Christian Gieger, Leif C Groop, Vilmundur Gudnason, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Aroon Hingorani, Joel N Hirschhorn, Albert Hofman, G Kees Hovingh, Chao Agnes Hsiung, Steve E Humphries, Steven C Hunt, Kristian Hveem, Carlos Iribarren, Marjo-Riitta Järvelin, Antti Jula, Mika Kähönen, Jaakko Kaprio, Antero Kesäniemi, Mika Kivimäki, Jaspal S Kooner, Peter J Koudstaal, Ronald M Krauss, Diana Kuh, Johanna Kuusisto, Kirsten O Kyvik, Markku Laakso, Timo A Lakka, Lars Lind, Cecilia M Lindgren, Nicholas G Martin, Winfried März, Mark I McCarthy, Colin A McKenzie, Pierre Meneton, Andres Metspalu, Leena Moilanen, Andrew D Morris, Patricia B Munroe, Inger Njølstad, Nancy L Pedersen, Chris Power, Peter P Pramstaller, Jackie F Price, Bruce M Psaty, Thomas Quertermous, Rainer Rauramaa, Danish Saleheen, Veikko Salomaa, Dharambir K Sanghera, Jouko Saramies, Peter E H Schwarz, Wayne H-H Sheu, Alan R Shuldiner, Agneta Siegbahn, Tim D Spector, Kari Stefansson, David P Strachan, Bamidele O Tayo, Elena Tremoli, Jaakko Tuomilehto, Matti Uusitupa, Cornelia M van Duijn, Peter Vollenweider, Lars Wallentin, Nicholas J Wareham, John B Whitfield, Bruce H R Wolffenbuttel, David Altshuler, José M Ordovás, Eric Boerwinkle, Colin N A Palmer, Unnur Thorsteinsdottir, Daniel I Chasman, Jerome I Rotter, Paul W Franks, Samuli Ripatti, L Adrienne Cupples, Manjinder S Sandhu, Stephen S Rich, Michael Boehnke, Panos Deloukas, Karen L Mohlke, Erik Ingelsson, Gonçalo R Abecasis, Mark J Daly, Benjamin M Neale, Sekar Kathiresan.
Nat. Genet.
PUBLISHED: 02-20-2013
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Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphisms effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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Comparing methods for performing trans-ethnic meta-analysis of genome-wide association studies.
Hum. Mol. Genet.
PUBLISHED: 02-12-2013
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Genome-wide association studies (GWASs) have discovered thousands of variants that are associated with human health and disease. Whilst early GWASs have primarily focused on genetically homogeneous populations of European, East Asian and South Asian ancestries, the next-generation genome-wide surveys are starting to pool studies from ethnically diverse populations within a single meta-analysis. However, classical epidemiological strategies for meta-analyses that assume fixed- or random-effects may not be the most suitable approaches to combine GWAS findings as these either confer low statistical power or identify mostly loci where the variants carry homogeneous effect sizes that are present in most of the studies. In a trans-ethnic meta-analysis, it is likely that some genetic loci will exhibit heterogeneous effect sizes across the populations. This may be due to differences in study designs, differences arising from the interactions with other genetic variants, or genuine biological differences attributed to environmental, dietary or lifestyle factors that modulate the influence of the genes. Here we compare different strategies for meta-analyzing GWAS across genetically diverse populations, where we intentionally vary the effect sizes present across the different populations. We subsequently applied the methods that yielded the highest statistical power to a trans-ethnic meta-analysis of seven GWAS in type 2 diabetes, and showed that these methods identified bona fide associations that would otherwise have been missed by the classical strategies.
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Prognostic value of energy loss index in asymptomatic aortic stenosis.
Circulation
PUBLISHED: 01-28-2013
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Aortic valve area index adjusted for pressure recovery (energy loss index [ELI]) has been suggested as a more accurate measure of aortic stenosis (AS) severity, but its prognostic value has not been determined in a prospective study.
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Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.
Diabetes
PUBLISHED: 01-08-2013
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We performed a genome-wide association study (GWAS) and a multistage meta-analysis of type 2 diabetes (T2D) in Punjabi Sikhs from India. Our discovery GWAS in 1,616 individuals (842 case subjects) was followed by in silico replication of the top 513 independent single nucleotide polymorphisms (SNPs) (P < 10?³) in Punjabi Sikhs (n = 2,819; 801 case subjects). We further replicated 66 SNPs (P < 10??) through genotyping in a Punjabi Sikh sample (n = 2,894; 1,711 case subjects). On combined meta-analysis in Sikh populations (n = 7,329; 3,354 case subjects), we identified a novel locus in association with T2D at 13q12 represented by a directly genotyped intronic SNP (rs9552911, P = 1.82 × 10??) in the SGCG gene. Next, we undertook in silico replication (stage 2b) of the top 513 signals (P < 10?³) in 29,157 non-Sikh South Asians (10,971 case subjects) and de novo genotyping of up to 31 top signals (P < 10??) in 10,817 South Asians (5,157 case subjects) (stage 3b). In combined South Asian meta-analysis, we observed six suggestive associations (P < 10?? to < 10??), including SNPs at HMG1L1/CTCFL, PLXNA4, SCAP, and chr5p11. Further evaluation of 31 top SNPs in 33,707 East Asians (16,746 case subjects) (stage 3c) and 47,117 Europeans (8,130 case subjects) (stage 3d), and joint meta-analysis of 128,127 individuals (44,358 case subjects) from 27 multiethnic studies, did not reveal any additional loci nor was there any evidence of replication for the new variant. Our findings provide new evidence on the presence of a population-specific signal in relation to T2D, which may provide additional insights into T2D pathogenesis.
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Ideology and prejudice: the role of value conflicts.
Psychol Sci
PUBLISHED: 01-03-2013
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In three studies, we tested whether prejudice derives from perceived similarities and dissimilarities in political ideologies (the value-conflict hypothesis). Across three diverse samples in study 1, conservatives had less favorable impressions than liberals of groups that were identified as liberal (e.g., African Americans, homosexuals), but more favorable impressions than liberals of groups identified as conservative (e.g., Christian fundamentalists, businesspeople). In studies 2 and 3, we independently manipulated a targets race (European American or African American) and political attitudes (liberal or conservative). Both studies found symmetrical preferences, with liberals and conservatives each liking attitudinally similar targets more than dissimilar targets. The amount of prejudice was comparable for liberals and conservatives, and the race of the target had no effect. In all three studies, the same patterns were obtained even after controlling for individual differences on prejudice-related dimensions (e.g., system justification, social-dominance orientation, modern racism). The patterns strongly support the value-conflict hypothesis and indicate that prejudice exists on both sides of the political spectrum.
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Repeated renal infarction in native and transplanted kidneys due to left ventricular thrombus formation caused by antiphospholipid antibody syndrome.
Int Med Case Rep J
PUBLISHED: 01-01-2013
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Antiphospholipid syndrome can be a feature of several underlying conditions, such as lupus, but it can also occur idiopathically. Diagnosis usually comes after investigation of recurrent venous or arterial thromboses, emboli, or hypertension/proteinuria where the kidney is involved and is usually confirmed by laboratory testing. We describe a case of a man with a myocardial infarction who developed mural thrombus in an akinetic left ventricular segment but then who recurrently embolized first to one of his native kidneys and then later to a transplanted kidney. Although the clinical behavior was typical of antiphospholipid syndrome, it took numerous laboratory assays over many years until finally the problem was confirmed and life-long warfarin therapy instituted.
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Fine-scale estimation of location of birth from genome-wide single-nucleotide polymorphism data.
Genetics
PUBLISHED: 11-17-2011
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Systematic nonrandom mating in populations results in genetic stratification and is predominantly caused by geographic separation, providing the opportunity to infer individuals birthplace from genetic data. Such inference has been demonstrated for individuals country of birth, but here we use data from the Northern Finland Birth Cohort 1966 (NFBC1966) to investigate the characteristics of genetic structure within a population and subsequently develop a method for inferring location to a finer scale. Principal component analysis (PCA) shows that while the first PCs are particularly informative for location, there is also location information in the higher-order PCs, but it cannot be captured by a linear model. We introduce a new method, pcLOCATE, which is able to exploit this information to improve the accuracy of location inference. pcLOCATE uses individuals PC values to estimate the probability of birth in each town and then averages over all towns to give an estimated longitude and latitude of birth using a fully Bayesian model. We apply pcLOCATE to the NFBC1966 data to estimate parental birthplace, testing with successively more PCs and finding the model with the top 23 PCs most accurate, with a median distance of 23 km between the estimated and the true location. pcLOCATE predicts the most recent residence of NFBC1966 individuals to a median distance of 47 km. We also apply pcLOCATE to Indian individuals from the London Life Sciences Prospective Population Study (LOLIPOP) data, and find that birthplace is predicated to a median distance of 54 km from the true location. A method with such accuracy is potentially valuable in population genetics and forensics.
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New gene functions in megakaryopoiesis and platelet formation.
Christian Gieger, Aparna Radhakrishnan, Ana Cvejic, Weihong Tang, Eleonora Porcu, Giorgio Pistis, Jovana Serbanovic-Canic, Ulrich Elling, Alison H Goodall, Yann Labrune, Lorna M Lopez, Reedik Mägi, Stuart Meacham, Yukinori Okada, Nicola Pirastu, Rossella Sorice, Alexander Teumer, Katrin Voss, Weihua Zhang, Ramiro Ramirez-Solis, Joshua C Bis, David Ellinghaus, Martin Gögele, Jouke-Jan Hottenga, Claudia Langenberg, Peter Kovacs, Paul F O'Reilly, So-Youn Shin, Tonu Esko, Jaana Hartiala, Stavroula Kanoni, Federico Murgia, Afshin Parsa, Jonathan Stephens, Pim van der Harst, C Ellen van der Schoot, Hooman Allayee, Antony Attwood, Beverley Balkau, François Bastardot, Saonli Basu, Sebastian E Baumeister, Ginevra Biino, Lorenzo Bomba, Amélie Bonnefond, Francois Cambien, John C Chambers, Francesco Cucca, Pio D'Adamo, Gail Davies, Rudolf A de Boer, Eco J C de Geus, Angela Döring, Paul Elliott, Jeanette Erdmann, David M Evans, Mario Falchi, Wei Feng, Aaron R Folsom, Ian H Frazer, Quince D Gibson, Nicole L Glazer, Chris Hammond, Anna-Liisa Hartikainen, Susan R Heckbert, Christian Hengstenberg, Micha Hersch, Thomas Illig, Ruth J F Loos, Jennifer Jolley, Kay Tee Khaw, Brigitte Kühnel, Marie-Christine Kyrtsonis, Vasiliki Lagou, Heather Lloyd-Jones, Thomas Lumley, Massimo Mangino, Andrea Maschio, Irene Mateo Leach, Barbara McKnight, Yasin Memari, Braxton D Mitchell, Grant W Montgomery, Yusuke Nakamura, Matthias Nauck, Gerjan Navis, Ute Nöthlings, Ilja M Nolte, David J Porteous, Anneli Pouta, Peter P Pramstaller, Janne Pullat, Susan M Ring, Jerome I Rotter, Daniela Ruggiero, Aimo Ruokonen, Cinzia Sala, Nilesh J Samani, Jennifer Sambrook, David Schlessinger, Stefan Schreiber, Heribert Schunkert, James Scott, Nicholas L Smith, Harold Snieder, John M Starr, Michael Stumvoll, Atsushi Takahashi, W H Wilson Tang, Kent Taylor, Albert Tenesa, Swee Lay Thein, Anke Tönjes, Manuela Uda, Sheila Ulivi, Dirk J van Veldhuisen, Peter M Visscher, Uwe Völker, H-Erich Wichmann, Kerri L Wiggins, Gonneke Willemsen, Tsun-Po Yang, Jing Hua Zhao, Paavo Zitting, John R Bradley, George V Dedoussis, Paolo Gasparini, Stanley L Hazen, Andres Metspalu, Mario Pirastu, Alan R Shuldiner, L Joost van Pelt, Jaap-Jan Zwaginga, Dorret I Boomsma, Ian J Deary, Andre Franke, Philippe Froguel, Santhi K Ganesh, Marjo-Riitta Järvelin, Nicholas G Martin, Christa Meisinger, Bruce M Psaty, Timothy D Spector, Nicholas J Wareham, Jan-Willem N Akkerman, Marina Ciullo, Panos Deloukas, Andreas Greinacher, Steve Jupe, Naoyuki Kamatani, Jyoti Khadake, Jaspal S Kooner, Josef Penninger, Inga Prokopenko, Derek Stemple, Daniela Toniolo, Lorenz Wernisch, Serena Sanna, Andrew A Hicks, Augusto Rendon, Manuel A Ferreira, Willem H Ouwehand, Nicole Soranzo.
Nature
PUBLISHED: 10-21-2011
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Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.
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Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.
Rona J Strawbridge, Josée Dupuis, Inga Prokopenko, Adam Barker, Emma Ahlqvist, Denis Rybin, John R Petrie, Mary E Travers, Nabila Bouatia-Naji, Antigone S Dimas, Alexandra Nica, Eleanor Wheeler, Han Chen, Benjamin F Voight, Jalal Taneera, Stavroula Kanoni, John F Peden, Fabiola Turrini, Stefan Gustafsson, Carina Zabena, Peter Almgren, David J P Barker, Daniel Barnes, Elaine M Dennison, Johan G Eriksson, Per Eriksson, Elodie Eury, Lasse Folkersen, Caroline S Fox, Timothy M Frayling, Anuj Goel, Harvest F Gu, Momoko Horikoshi, Bo Isomaa, Anne U Jackson, Karen A Jameson, Eero Kajantie, Julie Kerr-Conte, Teemu Kuulasmaa, Johanna Kuusisto, Ruth J F Loos, Jian'an Luan, Konstantinos Makrilakis, Alisa K Manning, María Teresa Martínez-Larrad, Narisu Narisu, Maria Nastase Mannila, John Ohrvik, Clive Osmond, Laura Pascoe, Felicity Payne, Avan A Sayer, Bengt Sennblad, Angela Silveira, Alena Stančáková, Kathy Stirrups, Amy J Swift, Ann-Christine Syvänen, Tiinamaija Tuomi, Ferdinand M van 't Hooft, Mark Walker, Michael N Weedon, Weijia Xie, Björn Zethelius, , Halit Ongen, Anders Malarstig, Jemma C Hopewell, Danish Saleheen, John Chambers, Sarah Parish, John Danesh, Jaspal Kooner, Claes-Göran Ostenson, Lars Lind, Cyrus C Cooper, Manuel Serrano-Ríos, Ele Ferrannini, Tom J Forsen, Robert Clarke, Maria Grazia Franzosi, Udo Seedorf, Hugh Watkins, Philippe Froguel, Paul Johnson, Panos Deloukas, Francis S Collins, Markku Laakso, Emmanouil T Dermitzakis, Michael Boehnke, Mark I McCarthy, Nicholas J Wareham, Leif Groop, François Pattou, Anna L Gloyn, George V Dedoussis, Valeriya Lyssenko, James B Meigs, Inês Barroso, Richard M Watanabe, Erik Ingelsson, Claudia Langenberg, Anders Hamsten, Jose C Florez.
Diabetes
PUBLISHED: 08-26-2011
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Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired ?-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology.
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The CryoLife-OBrien stentless replacement aortic valve: patterns of valve failure.
J. Heart Valve Dis.
PUBLISHED: 08-26-2011
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The study aim was to describe patterns of failure in a consecutive series of patients with the CryoLife-OBrien stentless porcine aortic bioprosthesis.
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Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
, Georg B Ehret, Patricia B Munroe, Kenneth M Rice, Murielle Bochud, Andrew D Johnson, Daniel I Chasman, Albert V Smith, Martin D Tobin, Germaine C Verwoert, Shih-Jen Hwang, Vasyl Pihur, Peter Vollenweider, Paul F O'Reilly, Najaf Amin, Jennifer L Bragg-Gresham, Alexander Teumer, Nicole L Glazer, Lenore Launer, Jing Hua Zhao, Yurii Aulchenko, Simon Heath, Siim Sõber, Afshin Parsa, Jian'an Luan, Pankaj Arora, Abbas Dehghan, Feng Zhang, Gavin Lucas, Andrew A Hicks, Anne U Jackson, John F Peden, Toshiko Tanaka, Sarah H Wild, Igor Rudan, Wilmar Igl, Yuri Milaneschi, Alex N Parker, Cristiano Fava, John C Chambers, Ervin R Fox, Meena Kumari, Min Jin Go, Pim van der Harst, Wen Hong Linda Kao, Marketa Sjögren, D G Vinay, Myriam Alexander, Yasuharu Tabara, Sue Shaw-Hawkins, Peter H Whincup, Yongmei Liu, Gang Shi, Johanna Kuusisto, Bamidele Tayo, Mark Seielstad, Xueling Sim, Khanh-Dung Hoang Nguyen, Terho Lehtimäki, Giuseppe Matullo, Ying Wu, Tom R Gaunt, N Charlotte Onland-Moret, Matthew N Cooper, Carl G P Platou, Elin Org, Rebecca Hardy, Santosh Dahgam, Jutta Palmen, Veronique Vitart, Peter S Braund, Tatiana Kuznetsova, Cuno S P M Uiterwaal, Adebowale Adeyemo, Walter Palmas, Harry Campbell, Barbara Ludwig, Maciej Tomaszewski, Ioanna Tzoulaki, Nicholette D Palmer, Thor Aspelund, Melissa Garcia, Yen-Pei C Chang, Jeffrey R O'Connell, Nanette I Steinle, Diederick E Grobbee, Dan E Arking, Sharon L Kardia, Alanna C Morrison, Dena Hernandez, Samer Najjar, Wendy L McArdle, David Hadley, Morris J Brown, John M Connell, Aroon D Hingorani, Ian N M Day, Debbie A Lawlor, John P Beilby, Robert W Lawrence, Robert Clarke, Jemma C Hopewell, Halit Ongen, Albert W Dreisbach, Yali Li, J Hunter Young, Joshua C Bis, Mika Kähönen, Jorma Viikari, Linda S Adair, Nanette R Lee, Ming-Huei Chen, Matthias Olden, Cristian Pattaro, Judith A Hoffman Bolton, Anna Köttgen, Sven Bergmann, Vincent Mooser, Nish Chaturvedi, Timothy M Frayling, Muhammad Islam, Tazeen H Jafar, Jeanette Erdmann, Smita R Kulkarni, Stefan R Bornstein, Jürgen Gräßler, Leif Groop, Benjamin F Voight, Johannes Kettunen, Philip Howard, Andrew Taylor, Simonetta Guarrera, Fulvio Ricceri, Valur Emilsson, Andrew Plump, Inês Barroso, Kay-Tee Khaw, Alan B Weder, Steven C Hunt, Yan V Sun, Richard N Bergman, Francis S Collins, Lori L Bonnycastle, Laura J Scott, Heather M Stringham, Leena Peltonen, Markus Perola, Erkki Vartiainen, Stefan-Martin Brand, Jan A Staessen, Thomas J Wang, Paul R Burton, María Soler Artigas, Yanbin Dong, Harold Snieder, Xiaoling Wang, Haidong Zhu, Kurt K Lohman, Megan E Rudock, Susan R Heckbert, Nicholas L Smith, Kerri L Wiggins, Ayo Doumatey, Daniel Shriner, Gudrun Veldre, Margus Viigimaa, Sanjay Kinra, Dorairaj Prabhakaran, Vikal Tripathy, Carl D Langefeld, Annika Rosengren, Dag S Thelle, Anna Maria Corsi, Andrew Singleton, Terrence Forrester, Gina Hilton, Colin A McKenzie, Tunde Salako, Naoharu Iwai, Yoshikuni Kita, Toshio Ogihara, Takayoshi Ohkubo, Tomonori Okamura, Hirotsugu Ueshima, Satoshi Umemura, Susana Eyheramendy, Thomas Meitinger, H-Erich Wichmann, Yoon Shin Cho, Hyung-Lae Kim, Jong-Young Lee, James Scott, Joban S Sehmi, Weihua Zhang, Bo Hedblad, Peter Nilsson, George Davey Smith, Andrew Wong, Narisu Narisu, Alena Stančáková, Leslie J Raffel, Jie Yao, Sekar Kathiresan, Christopher J O'Donnell, Stephen M Schwartz, M Arfan Ikram, W T Longstreth, Thomas H Mosley, Sudha Seshadri, Nick R G Shrine, Louise V Wain, Mario A Morken, Amy J Swift, Jaana Laitinen, Inga Prokopenko, Paavo Zitting, Jackie A Cooper, Steve E Humphries, John Danesh, Asif Rasheed, Anuj Goel, Anders Hamsten, Hugh Watkins, Stephan J L Bakker, Wiek H van Gilst, Charles S Janipalli, K Radha Mani, Chittaranjan S Yajnik, Albert Hofman, Francesco U S Mattace-Raso, Ben A Oostra, Ayse Demirkan, Aaron Isaacs, Fernando Rivadeneira, Edward G Lakatta, Marco Orrù, Angelo Scuteri, Mika Ala-Korpela, Antti J Kangas, Leo-Pekka Lyytikäinen, Pasi Soininen, Taru Tukiainen, Peter Würtz, Rick Twee-Hee Ong, Marcus Dörr, Heyo K Kroemer, Uwe Völker, Henry Völzke, Pilar Galán, Serge Hercberg, Mark Lathrop, Diana Zelenika, Panos Deloukas, Massimo Mangino, Tim D Spector, Guangju Zhai, James F Meschia, Michael A Nalls, Pankaj Sharma, Janos Terzic, M V Kranthi Kumar, Matthew Denniff, Ewa Zukowska-Szczechowska, Lynne E Wagenknecht, F Gerald R Fowkes, Fadi J Charchar, Peter E H Schwarz, Caroline Hayward, Xiuqing Guo, Charles Rotimi, Michiel L Bots, Eva Brand, Nilesh J Samani, Ozren Polašek, Philippa J Talmud, Fredrik Nyberg, Diana Kuh, Maris Laan, Kristian Hveem, Lyle J Palmer, Yvonne T van der Schouw, Juan P Casas, Karen L Mohlke, Paolo Vineis, Olli Raitakari, Santhi K Ganesh, Tien Y Wong, E Shyong Tai, Richard S Cooper, Markku Laakso, Dabeeru C Rao, Tamara B Harris, Richard W Morris, Anna F Dominiczak, Mika Kivimäki, Michael G Marmot, Tetsuro Miki, Danish Saleheen, Giriraj R Chandak, Josef Coresh, Gerjan Navis, Veikko Salomaa, Bok-Ghee Han, Xiaofeng Zhu, Jaspal S Kooner, Olle Melander, Paul M Ridker, Stefania Bandinelli, Ulf B Gyllensten, Alan F Wright, James F Wilson, Luigi Ferrucci, Martin Farrall, Jaakko Tuomilehto, Peter P Pramstaller, Roberto Elosua, Nicole Soranzo, Eric J G Sijbrands, David Altshuler, Ruth J F Loos, Alan R Shuldiner, Christian Gieger, Pierre Meneton, André G Uitterlinden, Nicholas J Wareham, Vilmundur Gudnason, Jerome I Rotter, Rainer Rettig, Manuela Uda, David P Strachan, Jacqueline C M Witteman, Anna-Liisa Hartikainen, Jacques S Beckmann, Eric Boerwinkle, Ramachandran S Vasan, Michael Boehnke, Martin G Larson, Marjo-Riitta Järvelin, Bruce M Psaty, Gonçalo R Abecasis, Aravinda Chakravarti, Paul Elliott, Cornelia M van Duijn, Christopher Newton-Cheh, Daniel Levy, Mark J Caulfield, Toby Johnson.
Nature
PUBLISHED: 07-28-2011
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Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (?140?mm?Hg systolic blood pressure or? ?90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
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South Asians have adverse cerebrovascular haemodynamics, despite equivalent blood pressure, compared with Europeans. This is due to their greater hyperglycaemia.
Int J Epidemiol
PUBLISHED: 06-30-2011
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South Asians have a 1.5-fold increased stroke mortality compared with Europeans, despite similar blood pressures (BP). We hypothesized that it is the greater hyperglycaemia in South Asians that increases stroke risk, by adversely affecting cerebrovascular haemodynamics.
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Localisation of SCN10A gene product Na(v)1.8 and novel pain-related ion channels in human heart.
Int Heart J
PUBLISHED: 06-08-2011
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We have shown that the gene SCN10A encoding the sodium channel Na(v)1.8 is a susceptibility factor for heart block and serious ventricular arrhythmia. Since Na(v)1.8 is known to be present in nerve fibres that mediate pain, it may be related to both cardiac pain and dysrhythmia. The localisation of Na(v)1.8 and other key nociceptive ion channels, including Na(v)1.7, Na(v)1.9, capsaicin receptor TRPV1, and purinergic receptor P2X(3), have not been reported in human heart. The aim of this study was to determine the distribution of Na(v)1.8, related sodium and other sensory channels in human cardiac tissue, and correlate their density with sympathetic nerves, regenerating nerves (GAP-43), and vascularity. Human heart atrial appendage tissues (n = 13) were collected during surgery for valve disease. Tissues were investigated by immunohistology using specific antibodies to Na(v)1.8 and other markers. Na(v)1.8 immunoreactivity was detected in nerve fibres and fascicles in the myocardium, often closely associated with small capillaries. Na(v)1.8 nerve fibres per mm(2) correlated significantly with vascular markers. Na(v)1.8-immunoreactivity was present also in cardiomyocytes with a similar distribution pattern to that seen with connexins, the specialised gap junction proteins of myocardial intercalated discs. Na(v)1.5-immunoreactivity was detected in cardiomyocytes but not in nerve fibres. Na(v)1.7, Na(v)1.9, TRPV1, P2X(3)/P2X(2), and GAP43 positive nerve fibres were relatively sparse, whereas sympathetic innervation and connexin43 were abundant. We conclude that sodium channel Na(v)1.8 is present in sensory nerves and cardiomyocytes of human heart. Na(v)1.8 and other pain channels provide new targets for the understanding and treatment of cardiac pain and dysrhythmia.
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Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.
Gunter Schumann, Lachlan J Coin, Anbarasu Lourdusamy, Pimphen Charoen, Karen H Berger, David Stacey, Sylvane Desrivières, Fazil A Aliev, Anokhi A Khan, Najaf Amin, Yurii S Aulchenko, Georgy Bakalkin, Stephan J Bakker, Beverley Balkau, Joline W Beulens, Ainhoa Bilbao, Rudolf A de Boer, Delphine Beury, Michiel L Bots, Elemi J Breetvelt, Stéphane Cauchi, Christine Cavalcanti-Proença, John C Chambers, Toni-Kim Clarke, Norbert Dahmen, Eco J De Geus, Danielle Dick, Francesca Ducci, Alanna Easton, Howard J Edenberg, Tonu Esko, Tõnu Esk, Alberto Fernandez-Medarde, Tatiana Foroud, Nelson B Freimer, Jean-Antoine Girault, Diederick E Grobbee, Simonetta Guarrera, Daniel F Gudbjartsson, Anna-Liisa Hartikainen, Andrew C Heath, Victor Hesselbrock, Albert Hofman, Jouke-Jan Hottenga, Matti K Isohanni, Jaakko Kaprio, Kay-Tee Khaw, Brigitte Kuehnel, Jaana Laitinen, Stéphane Lobbens, Jian'an Luan, Massimo Mangino, Matthieu Maroteaux, Giuseppe Matullo, Mark I McCarthy, Christian Mueller, Gerjan Navis, Mattijs E Numans, Alejandro Núñez, Dale R Nyholt, Charlotte N Onland-Moret, Ben A Oostra, Paul F O'Reilly, Miklós Palkovits, Brenda W Penninx, Silvia Polidoro, Anneli Pouta, Inga Prokopenko, Fulvio Ricceri, Eugenio Santos, Johannes H Smit, Nicole Soranzo, Kijoung Song, Ulla Sovio, Michael Stumvoll, Ida Surakk, Thorgeir E Thorgeirsson, Unnur Thorsteinsdottir, Claire Troakes, Thorarinn Tyrfingsson, Anke Tönjes, Cuno S Uiterwaal, André G Uitterlinden, Pim van der Harst, Yvonne T van der Schouw, Oliver Staehlin, Nicole Vogelzangs, Peter Vollenweider, Gérard Waeber, Nicholas J Wareham, Dawn M Waterworth, John B Whitfield, Erich H Wichmann, Gonneke Willemsen, Jacqueline C Witteman, Xin Yuan, Guangju Zhai, Jing H Zhao, Weihua Zhang, Nicholas G Martin, Andres Metspalu, Angela Doering, James Scott, Tim D Spector, Ruth J Loos, Dorret I Boomsma, Vincent Mooser, Leena Peltonen, Kari Stefansson, Cornelia M van Duijn, Paolo Vineis, Wolfgang H Sommer, Jaspal S Kooner, Rainer Spanagel, Ulrike A Heberlein, Marjo-Riitta Järvelin, Paul Elliott.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-06-2011
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Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of ?2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 × 10(-8) to P = 4 × 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.
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Does subclinical atherosclerosis burden identify the increased risk of cardiovascular disease mortality among United Kingdom Indian Asians? A population study.
Am. Heart J.
PUBLISHED: 03-22-2011
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Indian Asians living in the United Kingdom have a >50% higher risk of cardiovascular disease (CVD) death compared with native European whites. The mechanisms underlying their excess mortality are not clear, and there are no validated tools capable of identifying this increased risk. The burden of subclinical atherosclerosis detected in the carotid arteries is an established prognosticator for major CVD events. We hypothesized that the increased prevalence of CVD among Indian Asians would be reflected by their having a greater burden of subclinical carotid artery atherosclerosis compared with European whites.
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Massive thrombi on an implantable cardioverter-defibrillator lead in a patient with the antiphospholipid syndrome.
Europace
PUBLISHED: 03-21-2011
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A patient with the antiphospholipid syndrome, who was suboptimally anticoagulated, presented with two large thrombi attached to her implantable cardioverter-defibrillator lead. Anticoagulation was unsuccessful so, in view of the risk from embolization, the system was removed surgically and an epicardial system implanted to reduce the risk of future device-related thrombosis.
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Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
John C Chambers, Weihua Zhang, Joban Sehmi, Xinzhong Li, Mark N Wass, Pim van der Harst, Hilma Holm, Serena Sanna, Maryam Kavousi, Sebastian E Baumeister, Lachlan J Coin, Guohong Deng, Christian Gieger, Nancy L Heard-Costa, Jouke-Jan Hottenga, Brigitte Kühnel, Vinod Kumar, Vasiliki Lagou, Liming Liang, Jian'an Luan, Pedro Marques Vidal, Irene Mateo Leach, Paul F O'Reilly, John F Peden, Nilufer Rahmioglu, Pasi Soininen, Elizabeth K Speliotes, Xin Yuan, Gudmar Thorleifsson, Behrooz Z Alizadeh, Larry D Atwood, Ingrid B Borecki, Morris J Brown, Pimphen Charoen, Francesco Cucca, Debashish Das, Eco J C de Geus, Anna L Dixon, Angela Döring, Georg Ehret, Gudmundur I Eyjolfsson, Martin Farrall, Nita G Forouhi, Nele Friedrich, Wolfram Goessling, Daniel F Gudbjartsson, Tamara B Harris, Anna-Liisa Hartikainen, Simon Heath, Gideon M Hirschfield, Albert Hofman, Georg Homuth, Elina Hyppönen, Harry L A Janssen, Toby Johnson, Antti J Kangas, Ido P Kema, Jens P Kühn, Sandra Lai, Mark Lathrop, Markus M Lerch, Yun Li, T Jake Liang, Jing-Ping Lin, Ruth J F Loos, Nicholas G Martin, Miriam F Moffatt, Grant W Montgomery, Patricia B Munroe, Kiran Musunuru, Yusuke Nakamura, Christopher J O'Donnell, Isleifur Olafsson, Brenda W Penninx, Anneli Pouta, Bram P Prins, Inga Prokopenko, Ralf Puls, Aimo Ruokonen, Markku J Savolainen, David Schlessinger, Jeoffrey N L Schouten, Udo Seedorf, Srijita Sen-Chowdhry, Katherine A Siminovitch, Johannes H Smit, Timothy D Spector, Wenting Tan, Tanya M Teslovich, Taru Tukiainen, André G Uitterlinden, Melanie M van der Klauw, Ramachandran S Vasan, Chris Wallace, Henri Wallaschofski, H-Erich Wichmann, Gonneke Willemsen, Peter Würtz, Chun Xu, Laura M Yerges-Armstrong, , Gonçalo R Abecasis, Kourosh R Ahmadi, Dorret I Boomsma, Mark Caulfield, William O Cookson, Cornelia M van Duijn, Philippe Froguel, Koichi Matsuda, Mark I McCarthy, Christa Meisinger, Vincent Mooser, Kirsi H Pietiläinen, Gunter Schumann, Harold Snieder, Michael J E Sternberg, Ronald P Stolk, Howard C Thomas, Unnur Thorsteinsdottir, Manuela Uda, Gérard Waeber, Nicholas J Wareham, Dawn M Waterworth, Hugh Watkins, John B Whitfield, Jacqueline C M Witteman, Bruce H R Wolffenbuttel, Caroline S Fox, Mika Ala-Korpela, Kari Stefansson, Peter Vollenweider, Henry Völzke, Eric E Schadt, James Scott, Marjo-Riitta Järvelin, Paul Elliott, Jaspal S Kooner.
Nat. Genet.
PUBLISHED: 03-08-2011
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Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.
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Outcome of patients with low-gradient "severe" aortic stenosis and preserved ejection fraction.
Circulation
PUBLISHED: 02-14-2011
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Retrospective studies have suggested that patients with a low transvalvular gradient in the presence of an aortic valve area < 1.0 cm² and normal ejection fraction may represent a subgroup with an advanced stage of aortic valve disease, reduced stroke volume, and poor prognosis requiring early surgery. We therefore evaluated the outcome of patients with low-gradient "severe" stenosis (defined as aortic valve area < 1.0 cm² and mean gradient ? 40 mm Hg) in the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study.
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Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.
Louise V Wain, Germaine C Verwoert, Paul F O'Reilly, Gang Shi, Toby Johnson, Andrew D Johnson, Murielle Bochud, Kenneth M Rice, Peter Henneman, Albert V Smith, Georg B Ehret, Najaf Amin, Martin G Larson, Vincent Mooser, David Hadley, Marcus Dörr, Joshua C Bis, Thor Aspelund, Tonu Esko, A Cecile J W Janssens, Jing Hua Zhao, Simon Heath, Maris Laan, Jingyuan Fu, Giorgio Pistis, Jian'an Luan, Pankaj Arora, Gavin Lucas, Nicola Pirastu, Irene Pichler, Anne U Jackson, Rebecca J Webster, Feng Zhang, John F Peden, Helena Schmidt, Toshiko Tanaka, Harry Campbell, Wilmar Igl, Yuri Milaneschi, Jouke-Jan Hottenga, Veronique Vitart, Daniel I Chasman, Stella Trompet, Jennifer L Bragg-Gresham, Behrooz Z Alizadeh, John C Chambers, Xiuqing Guo, Terho Lehtimäki, Brigitte Kühnel, Lorna M Lopez, Ozren Polašek, Mladen Boban, Christopher P Nelson, Alanna C Morrison, Vasyl Pihur, Santhi K Ganesh, Albert Hofman, Suman Kundu, Francesco U S Mattace-Raso, Fernando Rivadeneira, Eric J G Sijbrands, André G Uitterlinden, Shih-Jen Hwang, Ramachandran S Vasan, Thomas J Wang, Sven Bergmann, Peter Vollenweider, Gérard Waeber, Jaana Laitinen, Anneli Pouta, Paavo Zitting, Wendy L McArdle, Heyo K Kroemer, Uwe Völker, Henry Völzke, Nicole L Glazer, Kent D Taylor, Tamara B Harris, Helene Alavere, Toomas Haller, Aime Keis, Mari-Liis Tammesoo, Yurii Aulchenko, Inês Barroso, Kay-Tee Khaw, Pilar Galán, Serge Hercberg, Mark Lathrop, Susana Eyheramendy, Elin Org, Siim Sõber, Xiaowen Lu, Ilja M Nolte, Brenda W Penninx, Tanguy Corre, Corrado Masciullo, Cinzia Sala, Leif Groop, Benjamin F Voight, Olle Melander, Christopher J O'Donnell, Veikko Salomaa, Adamo Pio D'adamo, Antonella Fabretto, Flavio Faletra, Sheila Ulivi, Fabiola M Del Greco, Maurizio Facheris, Francis S Collins, Richard N Bergman, John P Beilby, Joseph Hung, A William Musk, Massimo Mangino, So-Youn Shin, Nicole Soranzo, Hugh Watkins, Anuj Goel, Anders Hamsten, Pierre Gider, Marisa Loitfelder, Marion Zeginigg, Dena Hernandez, Samer S Najjar, Pau Navarro, Sarah H Wild, Anna Maria Corsi, Andrew Singleton, Eco J C de Geus, Gonneke Willemsen, Alex N Parker, Lynda M Rose, Brendan Buckley, David Stott, Marco Orrù, Manuela Uda, , Melanie M van der Klauw, Weihua Zhang, Xinzhong Li, James Scott, Yii-Der Ida Chen, Gregory L Burke, Mika Kähönen, Jorma Viikari, Angela Döring, Thomas Meitinger, Gail Davies, John M Starr, Valur Emilsson, Andrew Plump, Jan H Lindeman, Peter A C 't Hoen, Inke R König, Janine F Felix, Robert Clarke, Jemma C Hopewell, Halit Ongen, Monique Breteler, Stéphanie Debette, Anita L Destefano, Myriam Fornage, Gary F Mitchell, Nicholas L Smith, Hilma Holm, Kari Stefansson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Nilesh J Samani, Michael Preuss, Igor Rudan, Caroline Hayward, Ian J Deary, H-Erich Wichmann, Olli T Raitakari, Walter Palmas, Jaspal S Kooner, Ronald P Stolk, J Wouter Jukema, Alan F Wright, Dorret I Boomsma, Stefania Bandinelli, Ulf B Gyllensten, James F Wilson, Luigi Ferrucci, Reinhold Schmidt, Martin Farrall, Tim D Spector, Lyle J Palmer, Jaakko Tuomilehto, Arne Pfeufer, Paolo Gasparini, David Siscovick, David Altshuler, Ruth J F Loos, Daniela Toniolo, Harold Snieder, Christian Gieger, Pierre Meneton, Nicholas J Wareham, Ben A Oostra, Andres Metspalu, Lenore Launer, Rainer Rettig, David P Strachan, Jacques S Beckmann, Jacqueline C M Witteman, Jeanette Erdmann, Ko Willems van Dijk, Eric Boerwinkle, Michael Boehnke, Paul M Ridker, Marjo-Riitta Järvelin, Aravinda Chakravarti, Gonçalo R Abecasis, Vilmundur Gudnason, Christopher Newton-Cheh, Daniel Levy, Patricia B Munroe, Bruce M Psaty, Mark J Caulfield, Dabeeru C Rao, Martin D Tobin, Paul Elliott, Cornelia M van Duijn.
Nat. Genet.
PUBLISHED: 02-10-2011
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Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.
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Up-beat UK: a programme of research into the relationship between coronary heart disease and depression in primary care patients.
BMC Fam Pract
PUBLISHED: 01-27-2011
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Coronary heart disease and depression are both common health problems and by 2020 will be the two leading causes of disability worldwide. Depression has been found to be more common in patients with coronary heart disease but the nature of this relationship is uncertain. In the United Kingdom general practitioners are now being remunerated for case-finding for depression in patients with coronary heart disease, however it is unclear how general practitioners should manage these patients. We aim to explore the relationship between coronary heart disease and depression in a primary care population and to develop an intervention for patients with coronary heart disease and depression.
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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
Tuomas O Kilpeläinen, M Carola Zillikens, Alena Stančáková, Francis M Finucane, Janina S Ried, Claudia Langenberg, Weihua Zhang, Jacques S Beckmann, Jian'an Luan, Liesbeth Vandenput, Unnur Styrkarsdottir, Yanhua Zhou, Albert Vernon Smith, Jing-Hua Zhao, Najaf Amin, Sailaja Vedantam, So-Youn Shin, Talin Haritunians, Mao Fu, Mary F Feitosa, Meena Kumari, Bjarni V Halldórsson, Emmi Tikkanen, Massimo Mangino, Caroline Hayward, Ci Song, Alice M Arnold, Yurii S Aulchenko, Ben A Oostra, Harry Campbell, L Adrienne Cupples, Kathryn E Davis, Angela Döring, Gudny Eiriksdottir, Karol Estrada, José Manuel Fernández-Real, Melissa Garcia, Christian Gieger, Nicole L Glazer, Candace Guiducci, Albert Hofman, Steve E Humphries, Bo Isomaa, Leonie C Jacobs, Antti Jula, David Karasik, Magnus K Karlsson, Kay-Tee Khaw, Lauren J Kim, Mika Kivimäki, Norman Klopp, Brigitte Kühnel, Johanna Kuusisto, Yongmei Liu, Osten Ljunggren, Mattias Lorentzon, Robert N Luben, Barbara McKnight, Dan Mellström, Braxton D Mitchell, Vincent Mooser, Jose María Moreno, Satu Mannisto, Jeffery R O'Connell, Laura Pascoe, Leena Peltonen, Belén Peral, Markus Perola, Bruce M Psaty, Veikko Salomaa, David B Savage, Robert K Semple, Tatjana Skarić-Jurić, Gunnar Sigurdsson, Kijoung S Song, Timothy D Spector, Ann-Christine Syvänen, Philippa J Talmud, Gudmar Thorleifsson, Unnur Thorsteinsdottir, André G Uitterlinden, Cornelia M van Duijn, Antonio Vidal-Puig, Sarah H Wild, Alan F Wright, Deborah J Clegg, Eric Schadt, James F Wilson, Igor Rudan, Samuli Ripatti, Ingrid B Borecki, Alan R Shuldiner, Erik Ingelsson, John-Olov Jansson, Robert C Kaplan, Vilmundur Gudnason, Tamara B Harris, Leif Groop, Douglas P Kiel, Fernando Rivadeneira, Mark Walker, Inês Barroso, Peter Vollenweider, Gérard Waeber, John C Chambers, Jaspal S Kooner, Nicole Soranzo, Joel N Hirschhorn, Kari Stefansson, H-Erich Wichmann, Claes Ohlsson, Stephen O'Rahilly, Nicholas J Wareham, Elizabeth K Speliotes, Caroline S Fox, Markku Laakso, Ruth J F Loos.
Nat. Genet.
PUBLISHED: 01-18-2011
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Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ?2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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The CXCL16 A181V mutation selectively inhibits monocyte adhesion to CXCR6 but is not associated with human coronary heart disease.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 01-13-2011
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The chemokine CXCL16 serves as a scavenger receptor for oxidized low-density lipoprotein and as an adhesion molecule and chemoattractant for cells expressing the receptor CXCR6. A commonly occurring CXCL16 allele has been described containing 2 nonsynonymous single-nucleotide polymorphisms in complete linkage disequilibrium, although the effects on CXCL16 function are unknown. Here, we examined the effect of the single-nucleotide polymorphisms on CXCL16 function and assessed the association of the mutant allele with coronary heart disease (CHD).
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Aortic valve surgery: marked increases in volume and significant decreases in mechanical valve use--an analysis of 41,227 patients over 5 years from the Society for Cardiothoracic Surgery in Great Britain and Ireland National database.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 01-12-2011
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Aortic valve replacement is accepted as a standard treatment for aortic stenosis and regurgitation. To help plan the national requirement for conventional and catheter-based procedures, we have analyzed the Society for Cardiothoracic Surgery in Great Britain and Ireland audit database to look at changes in practice over time.
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Cardiac valve disease and low-dose dopamine agonist therapy: an artefact of reporting bias?
Clin. Endocrinol. (Oxf)
PUBLISHED: 01-05-2011
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Chronic low-dose cabergoline treatment for microprolactinoma may cause cardiac valve pathology, but the evidence is contradictory. We investigated whether the expectation of the echocardiographer could influence the report.
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Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.
Nat. Genet.
PUBLISHED: 01-04-2011
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We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.
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Incidence of aetiological subtypes of stroke in a multi-ethnic population based study: the South London Stroke Register.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 10-25-2010
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Stroke risk is higher in black ethnic groups compared with white. Although risk factors for stroke are known to differ between these populations, few population studies have reported on the risk of aetiological stroke subtypes in black ethnic populations.
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Ethnic and gender differences in the relationship between hostility and metabolic and autonomic risk factors for coronary heart disease.
Psychosom Med
PUBLISHED: 10-14-2010
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To examine the relationship between hostility and biological risk factors for coronary heart disease (CHD) in a population of white European and South Asian men and women living in the United Kingdom.
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Genetic variants influencing circulating lipid levels and risk of coronary artery disease.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 09-23-2010
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Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides.
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Common variants at 10 genomic loci influence hemoglobin A?(C) levels via glycemic and nonglycemic pathways.
Nicole Soranzo, Serena Sanna, Eleanor Wheeler, Christian Gieger, Dörte Radke, Josée Dupuis, Nabila Bouatia-Naji, Claudia Langenberg, Inga Prokopenko, Elliot Stolerman, Manjinder S Sandhu, Matthew M Heeney, Joseph M Devaney, Muredach P Reilly, Sally L Ricketts, Alexandre F R Stewart, Benjamin F Voight, Christina Willenborg, Benjamin Wright, David Altshuler, Dan Arking, Beverley Balkau, Daniel Barnes, Eric Boerwinkle, Bernhard Böhm, Amélie Bonnefond, Lori L Bonnycastle, Dorret I Boomsma, Stefan R Bornstein, Yvonne Böttcher, Suzannah Bumpstead, Mary Susan Burnett-Miller, Harry Campbell, Antonio Cao, John Chambers, Robert Clark, Francis S Collins, Josef Coresh, Eco J C de Geus, Mariano Dei, Panos Deloukas, Angela Döring, Josephine M Egan, Roberto Elosua, Luigi Ferrucci, Nita Forouhi, Caroline S Fox, Christopher Franklin, Maria Grazia Franzosi, Sophie Gallina, Anuj Goel, Jurgen Graessler, Harald Grallert, Andreas Greinacher, David Hadley, Alistair Hall, Anders Hamsten, Caroline Hayward, Simon Heath, Christian Herder, Georg Homuth, Jouke-Jan Hottenga, Rachel Hunter-Merrill, Thomas Illig, Anne U Jackson, Antti Jula, Marcus Kleber, Christopher W Knouff, Augustine Kong, Jaspal Kooner, Anna Köttgen, Peter Kovacs, Knut Krohn, Brigitte Kühnel, Johanna Kuusisto, Markku Laakso, Mark Lathrop, Cécile Lecoeur, Man Li, Mingyao Li, Ruth J F Loos, Jian'an Luan, Valeriya Lyssenko, Reedik Mägi, Patrik K E Magnusson, Anders Malarstig, Massimo Mangino, María Teresa Martínez-Larrad, Winfried März, Wendy L McArdle, Ruth McPherson, Christa Meisinger, Thomas Meitinger, Olle Melander, Karen L Mohlke, Vincent E Mooser, Mario A Morken, Narisu Narisu, David M Nathan, Matthias Nauck, Chris O'Donnell, Konrad Oexle, Nazario Olla, James S Pankow, Felicity Payne, John F Peden, Nancy L Pedersen, Leena Peltonen, Markus Perola, Ozren Polašek, Eleonora Porcu, Daniel J Rader, Wolfgang Rathmann, Samuli Ripatti, Ghislain Rocheleau, Michael Roden, Igor Rudan, Veikko Salomaa, Richa Saxena, David Schlessinger, Heribert Schunkert, Peter Schwarz, Udo Seedorf, Elizabeth Selvin, Manuel Serrano-Ríos, Peter Shrader, Angela Silveira, David Siscovick, Kjioung Song, Timothy D Spector, Kari Stefansson, Valgerdur Steinthorsdottir, David P Strachan, Rona Strawbridge, Michael Stumvoll, Ida Surakka, Amy J Swift, Toshiko Tanaka, Alexander Teumer, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Anke Tönjes, Gianluca Usala, Veronique Vitart, Henry Völzke, Henri Wallaschofski, Dawn M Waterworth, Hugh Watkins, H-Erich Wichmann, Sarah H Wild, Gonneke Willemsen, Gordon H Williams, James F Wilson, Juliane Winkelmann, Alan F Wright, , Carina Zabena, Jing Hua Zhao, Stephen E Epstein, Jeanette Erdmann, Hakon H Hakonarson, Sekar Kathiresan, Kay-Tee Khaw, Robert Roberts, Nilesh J Samani, Mark D Fleming, Robert Sladek, Goncalo Abecasis, Michael Boehnke, Philippe Froguel, Leif Groop, Mark I McCarthy, W H Linda Kao, Jose C Florez, Manuela Uda, Nicholas J Wareham, Inês Barroso, James B Meigs.
Diabetes
PUBLISHED: 09-21-2010
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Glycated hemoglobin (HbA?(c)), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA?(c). We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA?(c) levels.
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Mutational heterogeneity, modifier genes, and environmental influences contribute to phenotypic diversity of arrhythmogenic cardiomyopathy.
Circ Cardiovasc Genet
PUBLISHED: 06-22-2010
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Arrhythmogenic cardiomyopathy is one of the leading causes of sudden cardiac death in the < or =35-year age group. The broad phenotypic spectrum encompasses left-dominant and biventricular subtypes, characterized by early left ventricular involvement, as well as the classic right-dominant form, better known as arrhythmogenic right ventricular cardiomyopathy. Mendelian inheritance patterns are accompanied by incomplete penetrance and variable expressivity, the latter manifesting as diversity in morphology, arrhythmic burden, and clinical outcomes.
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Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR) gene.
PLoS Genet.
PUBLISHED: 06-17-2010
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Calcium has a pivotal role in biological functions, and serum calcium levels have been associated with numerous disorders of bone and mineral metabolism, as well as with cardiovascular mortality. Here we report results from a genome-wide association study of serum calcium, integrating data from four independent cohorts including a total of 12,865 individuals of European and Indian Asian descent. Our meta-analysis shows that serum calcium is associated with SNPs in or near the calcium-sensing receptor (CASR) gene on 3q13. The top hit with a p-value of 6.3 x 10(-37) is rs1801725, a missense variant, explaining 1.26% of the variance in serum calcium. This SNP had the strongest association in individuals of European descent, while for individuals of Indian Asian descent the top hit was rs17251221 (p = 1.1 x 10(-21)), a SNP in strong linkage disequilibrium with rs1801725. The strongest locus in CASR was shown to replicate in an independent Icelandic cohort of 4,126 individuals (p = 1.02 x 10(-4)). This genome-wide meta-analysis shows that common CASR variants modulate serum calcium levels in the adult general population, which confirms previous results in some candidate gene studies of the CASR locus. This study highlights the key role of CASR in calcium regulation.
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Impact of pressure recovery on echocardiographic assessment of asymptomatic aortic stenosis: a SEAS substudy.
JACC Cardiovasc Imaging
PUBLISHED: 06-15-2010
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The aim of this analysis was to assess the diagnostic importance of pressure recovery in evaluation of aortic stenosis (AS) severity.
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The distinct relationships of carotid plaque disease and carotid intima-media thickness with left ventricular function.
J Am Soc Echocardiogr
PUBLISHED: 05-26-2010
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Subclinical carotid atherosclerosis has been associated with impaired left ventricular (LV) function and the development of heart failure. Whether impaired LV function is related primarily to increased intima-media thickness (IMT) or burden of plaque disease or both remains to be determined.
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Treadmill exercise in apparently asymptomatic patients with moderate or severe aortic stenosis: relationship between cardiac index and revealed symptoms.
Heart
PUBLISHED: 04-29-2010
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To test whether symptoms revealed on exercise testing in patients with moderate or severe aortic stenosis are associated with changes in left ventricular systolic function and to investigate the ability of resting measures to predict peak cardiac index.
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Aortic stenosis and lipids: does intervention work?
Curr. Opin. Cardiol.
PUBLISHED: 04-24-2010
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Aortic stenosis is a common disorder affecting increasing numbers of elderly patients, which is associated with markedly increased cardiovascular morbidity and mortality. Both histological and epidemiological studies have suggested that the process of valve degeneration may resemble atherosclerosis. This review investigates the potential role of lipid-lowering therapy in its management.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.