JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Mitochondrial DNA Sequence Variation Associated With Peripheral Nerve Function in the Elderly.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 11-15-2014
Show Abstract
Hide Abstract
Mitochondrial dysfunction is a prominent hallmark of many sensory neuropathies. The purpose of this study was to assess the influence of mitochondrial DNA sequence variation on peripheral nerve function in the population-based Health, Aging, and Body Composition Study.
Related JoVE Video
Association of Serum Bicarbonate with Incident Functional Limitation in Older Adults.
Clin J Am Soc Nephrol
PUBLISHED: 11-09-2014
Show Abstract
Hide Abstract
Cross-sectional studies have found that low serum bicarbonate is associated with slower gait speed. Whether bicarbonate levels independently predict the development of functional limitation has not been previously studied. Whether bicarbonate was associated with incident persistent lower extremity functional limitation and whether the relationship differed in individuals with and without CKD were assessed in participants in the Health, Aging, and Body Composition study, a prospective study of well functioning older individuals DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Functional limitation was defined as difficulty in walking 0.25 miles or up 10 stairs on two consecutive reports 6 months apart in the same activity (stairs or walking). Kidney function was measured using eGFR by the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, and CKD was defined as an eGFR<60 ml/min per 1.73 m(2). Serum bicarbonate was measured using arterialized venous blood gas. Cox proportional hazards analysis was used to assess the association of bicarbonate (<23, 23-25.9, and ?26 mEq/L) with functional limitation. Mixed model linear regression was performed to assess the association of serum bicarbonate on change in gait speed over time.
Related JoVE Video
Brain Volume as an Integrated Marker for the Risk of Death in a Community-Based Sample: Age Gene/Environment Susceptibility-Reykjavik Study.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 11-01-2014
Show Abstract
Hide Abstract
Total brain volume is an integrated measure of health and may be an independent indicator of mortality risk independent of any one clinical or subclinical disease state. We investigate the association of brain volume to total and cause-specific mortality in a large nondemented stroke-free community-based cohort.
Related JoVE Video
Plasma Phospholipid PUFAs Are Associated with Greater Muscle and Knee Extension Strength but Not with Changes in Muscle Parameters in Older Adults.
J. Nutr.
PUBLISHED: 10-31-2014
Show Abstract
Hide Abstract
Muscle mass, intermuscular adipose tissue, and strength are important indicators of physical function. Dietary fatty acids (FAs) have been associated with muscle parameters such as larger size and higher strength, but large, population-based longitudinal data in older adults who are at risk of functional decline are lacking.
Related JoVE Video
Association of low-density lipoprotein cholesterol-related genetic variants with aortic valve calcium and incident aortic stenosis.
JAMA
PUBLISHED: 10-27-2014
Show Abstract
Hide Abstract
Plasma low-density lipoprotein cholesterol (LDL-C) has been associated with aortic stenosis in observational studies; however, randomized trials with cholesterol-lowering therapies in individuals with established valve disease have failed to demonstrate reduced disease progression.
Related JoVE Video
Sensory and Motor Peripheral Nerve Function and Longitudinal Changes in Quadriceps Strength.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 10-17-2014
Show Abstract
Hide Abstract
Poor peripheral nerve function is common in older adults and may be a risk factor for strength decline, although this has not been assessed longitudinally.
Related JoVE Video
Adipose Tissue, Muscle, and Function: Potential Mediators of Associations Between Body Weight and Mortality in Older Adults With Type 2 Diabetes.
Diabetes Care
PUBLISHED: 10-14-2014
Show Abstract
Hide Abstract
Studies in type 2 diabetes report both increased mortality for normal weight and no evidence of an obesity paradox. We aimed to examine whether adipose tissue, muscle size, and physical function, which are known to vary by weight, mediate associations between BMI and mortality.
Related JoVE Video
Mediation Analysis of Aortic Stiffness and Renal Microvascular Function.
J. Am. Soc. Nephrol.
PUBLISHED: 10-09-2014
Show Abstract
Hide Abstract
Aortic stiffening, assessed by carotid-femoral pulse wave velocity, is associated with CKD. Transmission of excessive flow pulsatility into the low-impedance renal microvasculature may mediate this association. However, direct analyses of macrovascular-microvascular relations in the kidney are limited. Using arterial tonometry, iohexol clearance, and magnetic resonance imaging, we related arterial stiffness, GFR, urinary albumin excretion, and potential mediators, including renal artery pulsatility index, renal vascular resistance, and arterial volume in the cortex, in 367 older adults (ages 72-92 years) participating in the Age, Gene/Environment Susceptibility-Reykjavik Study. In a model adjusted for age, sex, heart rate, and body size, aortic stiffness was related to GFR (Slope of regression B=-2.28±0.85 ml/min per SD, P=0.008) but not urine albumin (P=0.09). After accounting for pulsatility index, the relation between aortic stiffness and GFR was no longer significant (P=0.10). Mediation analysis showed that 34% of the relation between aortic stiffness and GFR was mediated by pulsatility index (95% confidence interval of indirect effect, -1.35 to -0.29). An additional 20% or 36% of the relation was mediated by lower arterial volume in the cortex or higher renal vascular resistance, respectively, when offered as mediators downstream from higher pulsatility index (95% confidence interval of indirect effect including arterial volume in the cortex, -2.22 to -0.40; 95% confidence interval of indirect effect including renal vascular resistance, -2.51 to -0.76). These analyses provide the first evidence that aortic stiffness may contribute to lower GFR by transferring excessive flow pulsatility into the susceptible renal microvasculature, leading to dynamic constriction or vessel loss.
Related JoVE Video
Association between Sleep Duration and Mortality Is Mediated by Markers of Inflammation and Health in Older Adults: The Health, Aging and Body Composition Study.
Sleep
PUBLISHED: 09-21-2014
Show Abstract
Hide Abstract
Inflammation may represent a common physiological pathway linking both short and long sleep duration to mortality. We evaluated inflammatory markers as mediators of the relationship between sleep duration and mortality in community-dwelling older adults.
Related JoVE Video
Performance on fast- and usual-paced 400-m walk tests in older adults: are they comparable?
Aging Clin Exp Res
PUBLISHED: 09-02-2014
Show Abstract
Hide Abstract
Fast- and usual-paced 400-m walking tests are often used to assess physical fitness or function, respectively, though it is not known how performance converges on these tests. This study aims to determine whether performance on the fast- and usual-paced 400-m walks varies based upon age and physical function.
Related JoVE Video
Birth size and brain function 75 years later.
Pediatrics
PUBLISHED: 09-01-2014
Show Abstract
Hide Abstract
There are several lines of evidence pointing to fetal and other early origins of diseases of the aging brain, but there are no data directly addressing the hypotheses in an older population. We investigated the association of fetal size to late-age measures of brain structure and function in a large cohort of older men and women and explored the modifying effect of education on these associations.
Related JoVE Video
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
Show Abstract
Hide Abstract
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.
Related JoVE Video
Longitudinal Systolic Blood Pressure Characteristics and Integrity of White Matter Tracts in a Cohort of Very Old Black and White Adults.
Am. J. Hypertens.
PUBLISHED: 08-26-2014
Show Abstract
Hide Abstract
We sought to determine which systolic blood pressure (SBP) characteristics are associated with reduced brain integrity and whether these associations are stronger for white or gray matter. We hypothesized that exposure to higher and variable SBP will be associated with lower structural integrity of both gray and white matter.
Related JoVE Video
Circulating sclerostin associated with vertebral bone marrow fat in older men but not women.
J. Clin. Endocrinol. Metab.
PUBLISHED: 08-21-2014
Show Abstract
Hide Abstract
Osteocyte activity is crucial to maintenance of bone quality. Sclerostin, an osteocyte product, inhibits bone formation, yet higher circulating sclerostin is associated with higher bone density (BMD). Bone marrow fat (MF) is associated with osteoporosis but little is known about the relationship between osteocyte activity and MF.
Related JoVE Video
Predicting human movement with multiple accelerometers using movelets.
Med Sci Sports Exerc
PUBLISHED: 08-19-2014
Show Abstract
Hide Abstract
The study aims were 1) to develop transparent algorithms that use short segments of training data for predicting activity types and 2) to compare the prediction performance of the proposed algorithms using single accelerometers and multiple accelerometers.
Related JoVE Video
Strength and Function Response to Clinical Interventions of Older Women Categorized by Weakness and Low Lean Mass Using Classifications From the Foundation for the National Institute of Health Sarcopenia Project.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 08-18-2014
Show Abstract
Hide Abstract
The Foundation for the National Institutes of Health Sarcopenia Project developed data-driven cut-points for clinically meaningful weakness and low lean body mass. This analysis describes strength and function response to interventions based on these classifications.
Related JoVE Video
The prevalence of aortic stenosis in the elderly in Iceland and predictions for the coming decades: The AGES-Reykjavík study.
Int. J. Cardiol.
PUBLISHED: 08-15-2014
Show Abstract
Hide Abstract
To evaluate the prevalence of significant aortic valve stenosis (AS) in a randomly selected study population of elderly individuals representing the general population of Iceland. Furthermore, to predict the number of individuals likely to have severe AS in the future.
Related JoVE Video
Vitamin D Insufficiency and Abnormal Hemoglobin A1c in Black and White Older Persons.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 08-11-2014
Show Abstract
Hide Abstract
Although vitamin D has been mechanistically linked to insulin secretion and sensitivity, it remains unclear whether low 25-hydroxyvitamin D levels confer an increased risk of impaired glucose metabolism. We evaluated the relationship between vitamin D insufficiency (25-hydroxyvitamin D < 20ng/mL) and abnormal hemoglobin A1c (A1c) (?6.5%) in community-dwelling older persons and examined whether this relationship differed according to race.
Related JoVE Video
A blunted diurnal cortisol response in the lower educated does not explain educational differences in coronary heart disease: Findings from the AGES-Reykjavik Study.
Soc Sci Med
PUBLISHED: 08-01-2014
Show Abstract
Hide Abstract
Lower educational attainment generally is a strong predictor of coronary heart disease (CHD). The underlying mechanisms of this effect are, however, less clear. One hypothesis is that stress related to limitations imposed by lower socioeconomic status elicits changes in hypothalamic-pituitary-adrenal axis functioning, which, in turn, increases risk of CHD. In a large cohort study, we examined whether educational attainment was related to risk of fatal and non-fatal CHD and the extent to which salivary cortisol mediated this relation independent of potential confounders, including lifestyles. Data came from 3723 participants aged 66 through 96 from the Age, Gene/Environment Susceptibility (AGES) - Reykjavik Study. Between 2002 and 2006, data were collected using questionnaires and examinations including morning and evening salivary samples. Hospital admission records and cause of death registries (ICD-9 and ICD-10 codes) were available until December 2009. Linear regression and Cox proportional hazards analyses were performed. Even after adjustment for potential confounders, including lifestyle, persons with lower educational attainment showed a blunted cortisol response and also greater risk of incident CHD. However, our data did not support the role of cortisol as a mediator in the association between education and CHD in an older sample (192).
Related JoVE Video
Association of Hearing Impairment and Mortality in Older Adults.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 07-16-2014
Show Abstract
Hide Abstract
Hearing impairment (HI) is highly prevalent in older adults and is associated with social isolation, depression, and risk of dementia. Whether HI is associated with broader downstream outcomes is unclear. We undertook this study to determine whether audiometric HI is associated with mortality in older adults.
Related JoVE Video
Weight change, body composition, and risk of mobility disability and mortality in older adults: a population-based cohort study.
J Am Geriatr Soc
PUBLISHED: 07-15-2014
Show Abstract
Hide Abstract
To examine associations between weight change, body composition, risk of mobility disability, and mortality in older adults.
Related JoVE Video
Pulse pressure relation to aortic and left ventricular structure in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study.
Hypertension
PUBLISHED: 07-14-2014
Show Abstract
Hide Abstract
High pulse pressure, a major cardiovascular risk factor, has been attributed to medial elastic fiber degeneration and aortic dilation, which transfers hemodynamic load to stiffer collagen. However, recent studies suggest higher pulse pressure is instead associated with smaller aortic diameter. Thus, we sought to elucidate relations of pulse pressure with aortic stiffness and aortic and cardiac dimensions. We used magnetic resonance imaging to examine relationships of pulse pressure with lumen area and wall stiffness and thickness in the thoracic aorta and left ventricular structure in 526 participants (72-94 years of age, 295 women) in the community-based Age, Gene/Environment Susceptibility-Reykjavik Study. In a multivariable model that adjusted for age, sex, height, weight, and standard vascular risk factors, central pulse pressure had a negative relationship with aortic lumen area (all effects expressed as mm Hg/SD; B=-8.1±1.2; P<0.001) and positive relationships with left ventricular end-diastolic volume (B=3.8±1.0; P<0.001), carotid-femoral pulse wave velocity (B=3.6±1.0; P<0.001), and aortic wall area (B=3.0±1.2; P=0.015). Higher pulse pressure in older people is associated with smaller aortic lumen area and greater aortic wall stiffness and thickness and left ventricular volume. Relationships of larger ventricular volume and smaller aortic lumen with higher pulse pressure suggest mismatch in hemodynamic load accommodation by the heart and aorta in older people.
Related JoVE Video
The Alcohol Paradox: Light-to-Moderate Alcohol Consumption, Cognitive Function, and Brain Volume.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 07-02-2014
Show Abstract
Hide Abstract
Studies of older persons show consumption of light-to-moderate amounts of alcohol is positively associated with cognitive function and, separately, is negatively associated with total brain volume (TBV). This is paradoxical as generally, cognitive function is positively associated with TBV. We examined the relationships of TBV, global cognitive function (GCF), and alcohol consumption in a population-based cohort of 3,363 men and women (b. 1907-1935) participating in the Age Gene/Environment Susceptibility-Reykjavik Study (2002-2006) and who were free of dementia or mild cognitive impairment
Related JoVE Video
Apolipoprotein E Allele and Hearing Thresholds in Older Adults.
Am J Alzheimers Dis Other Demen
PUBLISHED: 06-08-2014
Show Abstract
Hide Abstract
Whether apolipoprotein E (APOE) E4 allele status which is associated with an increased risk of cognitive decline is also associated with hearing impairment is unknown.
Related JoVE Video
Joint effect of mid- and late-life blood pressure on the brain: the AGES-Reykjavik study.
Neurology
PUBLISHED: 06-04-2014
Show Abstract
Hide Abstract
We hypothesized that in participants with a history of hypertension, lower late-life blood pressure (BP) will be associated with more brain pathology.
Related JoVE Video
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
John R B Perry, Felix Day, Cathy E Elks, Patrick Sulem, Deborah J Thompson, Teresa Ferreira, Chunyan He, Daniel I Chasman, Tonu Esko, Gudmar Thorleifsson, Eva Albrecht, Wei Q Ang, Tanguy Corre, Diana L Cousminer, Bjarke Feenstra, Nora Franceschini, Andrea Ganna, Andrew D Johnson, Sanela Kjellqvist, Kathryn L Lunetta, George McMahon, Ilja M Nolte, Lavinia Paternoster, Eleonora Porcu, Albert V Smith, Lisette Stolk, Alexander Teumer, Natalia Tšernikova, Emmi Tikkanen, Sheila Ulivi, Erin K Wagner, Najaf Amin, Laura J Bierut, Enda M Byrne, Jouke-Jan Hottenga, Daniel L Koller, Massimo Mangino, Tune H Pers, Laura M Yerges-Armstrong, Jing Hua Zhao, Irene L Andrulis, Hoda Anton-Culver, Femke Atsma, Stefania Bandinelli, Matthias W Beckmann, Javier Benitez, Carl Blomqvist, Stig E Bojesen, Manjeet K Bolla, Bernardo Bonanni, Hiltrud Brauch, Hermann Brenner, Julie E Buring, Jenny Chang-Claude, Stephen Chanock, Jinhui Chen, Georgia Chenevix-Trench, J Margriet Collée, Fergus J Couch, David Couper, Andrea D Coviello, Angela Cox, Kamila Czene, Adamo Pio D'adamo, George Davey Smith, Immaculata De Vivo, Ellen W Demerath, Joe Dennis, Peter Devilee, Aida K Dieffenbach, Alison M Dunning, Gudny Eiriksdottir, Johan G Eriksson, Peter A Fasching, Luigi Ferrucci, Dieter Flesch-Janys, Henrik Flyger, Tatiana Foroud, Lude Franke, Melissa E Garcia, Montserrat Garcia-Closas, Frank Geller, Eco E J de Geus, Graham G Giles, Daniel F Gudbjartsson, Vilmundur Gudnason, Pascal Guénel, Suiqun Guo, Per Hall, Ute Hamann, Robin Haring, Catharina A Hartman, Andrew C Heath, Albert Hofman, Maartje J Hooning, John L Hopper, Frank B Hu, David J Hunter, David Karasik, Douglas P Kiel, Julia A Knight, Veli-Matti Kosma, Zoltan Kutalik, Sandra Lai, Diether Lambrechts, Annika Lindblom, Reedik Mägi, Patrik K Magnusson, Arto Mannermaa, Nicholas G Martin, Gisli Masson, Patrick F McArdle, Wendy L McArdle, Mads Melbye, Kyriaki Michailidou, Evelin Mihailov, Lili Milani, Roger L Milne, Heli Nevanlinna, Patrick Neven, Ellen A Nohr, Albertine J Oldehinkel, Ben A Oostra, Aarno Palotie, Munro Peacock, Nancy L Pedersen, Paolo Peterlongo, Julian Peto, Paul D P Pharoah, Dirkje S Postma, Anneli Pouta, Katri Pylkäs, Paolo Radice, Susan Ring, Fernando Rivadeneira, Antonietta Robino, Lynda M Rose, Anja Rudolph, Veikko Salomaa, Serena Sanna, David Schlessinger, Marjanka K Schmidt, Mellissa C Southey, Ulla Sovio, Meir J Stampfer, Doris Stöckl, Anna M Storniolo, Nicholas J Timpson, Jonathan Tyrer, Jenny A Visser, Peter Vollenweider, Henry Völzke, Gérard Waeber, Melanie Waldenberger, Henri Wallaschofski, Qin Wang, Gonneke Willemsen, Robert Winqvist, Bruce H R Wolffenbuttel, Margaret J Wright, , Dorret I Boomsma, Michael J Econs, Kay-Tee Khaw, Ruth J F Loos, Mark I McCarthy, Grant W Montgomery, John P Rice, Elizabeth A Streeten, Unnur Thorsteinsdottir, Cornelia M van Duijn, Behrooz Z Alizadeh, Sven Bergmann, Eric Boerwinkle, Heather A Boyd, Laura Crisponi, Paolo Gasparini, Christian Gieger, Tamara B Harris, Erik Ingelsson, Marjo-Riitta Järvelin, Peter Kraft, Debbie Lawlor, Andres Metspalu, Craig E Pennell, Paul M Ridker, Harold Snieder, Thorkild I A Sørensen, Tim D Spector, David P Strachan, André G Uitterlinden, Nicholas J Wareham, Elisabeth Widén, Marek Zygmunt, Anna Murray, Douglas F Easton, Kari Stefansson, Joanne M Murabito, Ken K Ong.
Nature
PUBLISHED: 05-30-2014
Show Abstract
Hide Abstract
Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P?
Related JoVE Video
Association of total adiposity and computed tomographic measures of regional adiposity with incident cancer risk: a prospective population-based study of older adults.
Appl Physiol Nutr Metab
PUBLISHED: 05-30-2014
Show Abstract
Hide Abstract
Obesity is associated with increased risk of many types of cancer. Less is known regarding associations between adipose depots and cancer risk. We aimed to explore relationships between adipose depots, risk of cancer, and obesity-related cancer (per NCI definition) in participants initially aged 70-79 years without prevalent cancer (1179 men, 1340 women), and followed for incident cancer for 13 years. Measures included body mass index (BMI), total adipose tissue from dual-energy X-ray absorptiometry, and computed tomography measures of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, thigh intermuscular adipose tissue, and thigh muscle attenuation (Hounsfield unit, HU), where low HU indicates fatty infiltration. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models adjusted for demographics, lifestyle variables, and medical conditions. During follow-up, 617 participants developed cancer of which 224 were obesity-related cancers. Total adipose tissue and VAT were positively associated with cancer risk among women (HR 1.14, 95% CI 1.01-1.30 per SD increase; HR 1.15, 95% CI 1.02-1.30 per SD increase). There were no associations with cancer risk among men. Total adipose tissue was positively associated with obesity-related cancer risk among women (HR 1.23, 95% CI 1.03-1.46 per SD increase). VAT was positively associated with obesity-related cancer risk among men (HR 1.30, 95% CI 1.06-1.60 per SD increase) and remained associated even with adjustment for BMI (HR 1.40, 95% CI 1.08-1.82 per SD increase). These findings provide insight into relationships between specific adipose depots and cancer risk and suggest differential relationships among men and women.
Related JoVE Video
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
Dan E Arking, Sara L Pulit, Lia Crotti, Pim van der Harst, Patricia B Munroe, Tamara T Koopmann, Nona Sotoodehnia, Elizabeth J Rossin, Michael Morley, Xinchen Wang, Andrew D Johnson, Alicia Lundby, Daniel F Gudbjartsson, Peter A Noseworthy, Mark Eijgelsheim, Yuki Bradford, Kirill V Tarasov, Marcus Dörr, Martina Müller-Nurasyid, Annukka M Lahtinen, Ilja M Nolte, Albert Vernon Smith, Joshua C Bis, Aaron Isaacs, Stephen J Newhouse, Daniel S Evans, Wendy S Post, Daryl Waggott, Leo-Pekka Lyytikäinen, Andrew A Hicks, Lewin Eisele, David Ellinghaus, Caroline Hayward, Pau Navarro, Sheila Ulivi, Toshiko Tanaka, David J Tester, Stéphanie Chatel, Stefan Gustafsson, Meena Kumari, Richard W Morris, Asa T Naluai, Sandosh Padmanabhan, Alexander Kluttig, Bernhard Strohmer, Andrie G Panayiotou, Maria Torres, Michael Knoflach, Jaroslav A Hubacek, Kamil Slowikowski, Soumya Raychaudhuri, Runjun D Kumar, Tamara B Harris, Lenore J Launer, Alan R Shuldiner, Alvaro Alonso, Joel S Bader, Georg Ehret, Hailiang Huang, W H Linda Kao, James B Strait, Peter W Macfarlane, Morris Brown, Mark J Caulfield, Nilesh J Samani, Florian Kronenberg, Johann Willeit, , J Gustav Smith, Karin H Greiser, Henriette Meyer zu Schwabedissen, Karl Werdan, Massimo Carella, Leopoldo Zelante, Susan R Heckbert, Bruce M Psaty, Jerome I Rotter, Ivana Kolčić, Ozren Polašek, Alan F Wright, Maura Griffin, Mark J Daly, David O Arnar, Hilma Holm, Unnur Thorsteinsdottir, Joshua C Denny, Dan M Roden, Rebecca L Zuvich, Valur Emilsson, Andrew S Plump, Martin G Larson, Christopher J O'Donnell, Xiaoyan Yin, Marco Bobbo, Adamo P d'Adamo, AnnaMaria Iorio, Gianfranco Sinagra, Angel Carracedo, Steven R Cummings, Michael A Nalls, Antti Jula, Kimmo K Kontula, Annukka Marjamaa, Lasse Oikarinen, Markus Perola, Kimmo Porthan, Raimund Erbel, Per Hoffmann, Karl-Heinz Jöckel, Hagen Kälsch, Markus M Nöthen, Marcel den Hoed, Ruth J F Loos, Dag S Thelle, Christian Gieger, Thomas Meitinger, Siegfried Perz, Annette Peters, Hanna Prucha, Moritz F Sinner, Melanie Waldenberger, Rudolf A de Boer, Lude Franke, Pieter A van der Vleuten, Britt Maria Beckmann, Eimo Martens, Abdennasser Bardai, Nynke Hofman, Arthur A M Wilde, Elijah R Behr, Chrysoula Dalageorgou, John R Giudicessi, Argelia Medeiros-Domingo, Julien Barc, Florence Kyndt, Vincent Probst, Alice Ghidoni, Roberto Insolia, Robert M Hamilton, Stephen W Scherer, Jeffrey Brandimarto, Kenneth Margulies, Christine E Moravec, Fabiola Del Greco M, Christian Fuchsberger, Jeffrey R O'Connell, Wai K Lee, Graham C M Watt, Harry Campbell, Sarah H Wild, Nour E El Mokhtari, Norbert Frey, Folkert W Asselbergs, Irene Mateo Leach, Gerjan Navis, Maarten P van den Berg, Dirk J van Veldhuisen, Manolis Kellis, Bouwe P Krijthe, Oscar H Franco, Albert Hofman, Jan A Kors, André G Uitterlinden, Jacqueline C M Witteman, Lyudmyla Kedenko, Claudia Lamina, Ben A Oostra, Gonçalo R Abecasis, Edward G Lakatta, Antonella Mulas, Marco Orrù, David Schlessinger, Manuela Uda, Marcello R P Markus, Uwe Völker, Harold Snieder, Timothy D Spector, Johan Arnlöv, Lars Lind, Johan Sundström, Ann-Christine Syvänen, Mika Kivimäki, Mika Kähönen, Nina Mononen, Olli T Raitakari, Jorma S Viikari, Vera Adamkova, Stefan Kiechl, María Brión, Andrew N Nicolaides, Bernhard Paulweber, Johannes Haerting, Anna F Dominiczak, Fredrik Nyberg, Peter H Whincup, Aroon D Hingorani, Jean-Jacques Schott, Connie R Bezzina, Erik Ingelsson, Luigi Ferrucci, Paolo Gasparini, James F Wilson, Igor Rudan, Andre Franke, Thomas W Mühleisen, Peter P Pramstaller, Terho J Lehtimäki, Andrew D Paterson, Afshin Parsa, Yongmei Liu, Cornelia M van Duijn, David S Siscovick, Vilmundur Gudnason, Yalda Jamshidi, Veikko Salomaa, Stephan B Felix, Serena Sanna, Marylyn D Ritchie, Bruno H Stricker, Kari Stefansson, Laurie A Boyer, Thomas P Cappola, Jesper V Olsen, Kasper Lage, Peter J Schwartz, Stefan Kääb, Aravinda Chakravarti, Michael J Ackerman, Arne Pfeufer, Paul I W de Bakker, Christopher Newton-Cheh.
Nat. Genet.
PUBLISHED: 05-29-2014
Show Abstract
Hide Abstract
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ?8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
Related JoVE Video
Trajectories of inflammatory markers and cognitive decline over 10 years.
Neurobiol. Aging
PUBLISHED: 05-22-2014
Show Abstract
Hide Abstract
We aimed to examine trajectories of inflammatory markers and cognitive decline over 10 years. Cox proportional hazards models were used to examine the association between interleukin-6 and C-reactive protein (CRP) trajectory components (slope, variability, and baseline level) and cognitive decline among 1323 adults, aged 70-79 years in the Health, Aging, and Body Composition Study. We tested for interactions by sex and apolipoprotein E (APOE) genotype. In models adjusted for multiple covariates and comorbidities, extreme CRP variability was significantly associated with cognitive decline (hazard ratio [HR] 1.6, 95% confidence interval [CI]: 1.1-2.3). This association was modified by sex and APOE e4 (p < 0.001 for both), such that the association remained among women (HR = 1.8; 95% CI: 1.1, 3.0) and among those with no APOE e4 allele (HR = 1.6; 95% CI: 1.1, 2.5). There were no significant associations between slope or baseline level of CRP and cognitive decline nor between interleukin-6 and cognitive decline. We believe CRP variability likely reflects poor control of or greater changes in vascular or metabolic disease over time, which in turn is associated with cognitive decline.
Related JoVE Video
Genome-wide association analysis identifies six new loci associated with forced vital capacity.
Daan W Loth, María Soler Artigas, Sina A Gharib, Louise V Wain, Nora Franceschini, Beate Koch, Tess D Pottinger, Albert Vernon Smith, Qing Duan, Chris Oldmeadow, Mi Kyeong Lee, David P Strachan, Alan L James, Jennifer E Huffman, Veronique Vitart, Adaikalavan Ramasamy, Nicholas J Wareham, Jaakko Kaprio, Xin-Qun Wang, Holly Trochet, Mika Kähönen, Claudia Flexeder, Eva Albrecht, Lorna M Lopez, Kim de Jong, Bharat Thyagarajan, Alexessander Couto Alves, Stefan Enroth, Ernst Omenaas, Peter K Joshi, Tove Fall, Ana Viñuela, Lenore J Launer, Laura R Loehr, Myriam Fornage, Guo Li, Jemma B Wilk, Wenbo Tang, Ani Manichaikul, Lies Lahousse, Tamara B Harris, Kari E North, Alicja R Rudnicka, Jennie Hui, Xiangjun Gu, Thomas Lumley, Alan F Wright, Nicholas D Hastie, Susan Campbell, Rajesh Kumar, Isabelle Pin, Robert A Scott, Kirsi H Pietiläinen, Ida Surakka, Yongmei Liu, Elizabeth G Holliday, Holger Schulz, Joachim Heinrich, Gail Davies, Judith M Vonk, Mary Wojczynski, Anneli Pouta, Asa Johansson, Sarah H Wild, Erik Ingelsson, Fernando Rivadeneira, Henry Völzke, Pirro G Hysi, Gudny Eiriksdottir, Alanna C Morrison, Jerome I Rotter, Wei Gao, Dirkje S Postma, Wendy B White, Stephen S Rich, Albert Hofman, Thor Aspelund, David Couper, Lewis J Smith, Bruce M Psaty, Kurt Lohman, Esteban G Burchard, André G Uitterlinden, Melissa Garcia, Bonnie R Joubert, Wendy L McArdle, A Bill Musk, Nadia Hansel, Susan R Heckbert, Lina Zgaga, Joyce B J van Meurs, Pau Navarro, Igor Rudan, Yeon-Mok Oh, Susan Redline, Deborah L Jarvis, Jing Hua Zhao, Taina Rantanen, George T O'Connor, Samuli Ripatti, Rodney J Scott, Stefan Karrasch, Harald Grallert, Nathan C Gaddis, John M Starr, Cisca Wijmenga, Ryan L Minster, David J Lederer, Juha Pekkanen, Ulf Gyllensten, Harry Campbell, Andrew P Morris, Sven Gläser, Christopher J Hammond, Kristin M Burkart, John Beilby, Stephen B Kritchevsky, Vilmundur Gudnason, Dana B Hancock, O Dale Williams, Ozren Polašek, Tatijana Zemunik, Ivana Kolčić, Marcy F Petrini, Matthias Wjst, Woo Jin Kim, David J Porteous, Generation Scotland, Blair H Smith, Anne Viljanen, Markku Heliövaara, John R Attia, Ian Sayers, Regina Hampel, Christian Gieger, Ian J Deary, H Marike Boezen, Anne Newman, Marjo-Riitta Järvelin, James F Wilson, Lars Lind, Bruno H Stricker, Alexander Teumer, Timothy D Spector, Erik Melén, Marjolein J Peters, Leslie A Lange, R Graham Barr, Ken R Bracke, Fien M Verhamme, Joohon Sung, Pieter S Hiemstra, Patricia A Cassano, Akshay Sood, Caroline Hayward, Josée Dupuis, Ian P Hall, Guy G Brusselle, Martin D Tobin, Stephanie J London.
Nat. Genet.
PUBLISHED: 05-22-2014
Show Abstract
Hide Abstract
Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
Related JoVE Video
Can change in prolonged walking be inferred from a short test of gait speed among older adults who are initially well-functioning?
Phys Ther
PUBLISHED: 05-01-2014
Show Abstract
Hide Abstract
The ability to walk for short and prolonged periods of time is often measured with separate walking tests. It is unclear whether decline in the 2-minute walk coincides with decline in a shorter 20-m walk among older adults.
Related JoVE Video
An evidence-based comparison of operational criteria for the presence of sarcopenia.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 04-17-2014
Show Abstract
Hide Abstract
Several consensus groups have previously published operational criteria for sarcopenia, incorporating lean mass with strength and/or physical performance. The purpose of this manuscript is to describe the prevalence, agreement, and discrepancies between the Foundation for the National Institutes of Health (FNIH) criteria with other operational definitions for sarcopenia.
Related JoVE Video
Criteria for clinically relevant weakness and low lean mass and their longitudinal association with incident mobility impairment and mortality: the foundation for the National Institutes of Health (FNIH) sarcopenia project.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 04-17-2014
Show Abstract
Hide Abstract
This analysis sought to determine the associations of the Foundation for the National Institutes of Health Sarcopenia Project criteria for weakness and low lean mass with likelihood for mobility impairment (gait speed ? 0.8 m/s) and mortality. Providing validity for these criteria is essential for research and clinical evaluation.
Related JoVE Video
Cutpoints for low appendicular lean mass that identify older adults with clinically significant weakness.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 04-17-2014
Show Abstract
Hide Abstract
Low lean mass is potentially clinically important in older persons, but criteria have not been empirically validated. As part of the FNIH (Foundation for the National Institutes of Health) Sarcopenia Project, this analysis sought to identify cutpoints in lean mass by dual-energy x-ray absorptiometry that discriminate the presence or absence of weakness (defined in a previous report in the series as grip strength <26kg in men and <16kg in women).
Related JoVE Video
Grip strength cutpoints for the identification of clinically relevant weakness.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 04-17-2014
Show Abstract
Hide Abstract
Weakness is common and contributes to disability, but no consensus exists regarding a strength cutpoint to identify persons at high risk. This analysis, conducted as part of the Foundation for the National Institutes of Health Sarcopenia Project, sought to identify cutpoints that distinguish weakness associated with mobility impairment, defined as gait speed less than 0.8 m/s.
Related JoVE Video
The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 04-17-2014
Show Abstract
Hide Abstract
Low muscle mass and weakness are common and potentially disabling in older adults, but in order to become recognized as a clinical condition, criteria for diagnosis should be based on clinically relevant thresholds and independently validated. The Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project used an evidence-based approach to develop these criteria. Initial findings were presented at a conference in May 2012, which generated recommendations that guided additional analyses to determine final recommended criteria. Details of the Project and its findings are presented in four accompanying manuscripts.
Related JoVE Video
Structural MRI correlates of apathy symptoms in older persons without dementia: AGES-Reykjavik Study.
Neurology
PUBLISHED: 04-16-2014
Show Abstract
Hide Abstract
We aimed to investigate the relation between apathy symptoms and structural brain changes on MRI, including white matter lesions (WMLs) and atrophy, in a large cohort of older persons.
Related JoVE Video
Higher step length variability indicates lower gray matter integrity of selected regions in older adults.
Gait Posture
PUBLISHED: 03-24-2014
Show Abstract
Hide Abstract
Step length variability (SLV) increases with age in those without overt neurologic disease, is higher in neurologic patients, is associated with falls, and predicts dementia. Whether higher SLV in older adults without neurologic disease indicates presence of neurologic abnormalities is unknown. Our objective was to identify whether SLV in older adults without overt disease is associated with findings from multimodal neuroimaging. A well-characterized cohort of 265 adults (79-90 years) was concurrently assessed by gait mat, magnetic resonance imaging with diffusion tensor, and neurological exam. Linear regression models adjusted for gait speed, demographic, health, and functional covariates assessed associations of MRI measures (gray matter volume, white matter hyperintensity volume, mean diffusivity, fractional anisotropy) with SLV. Regional distribution of associations was assessed by sparse partial least squares analyses. Higher SLV (mean: 8.4, SD: 3.3) was significantly associated with older age, slower gait speed, and poorer executive function and also with lower gray matter integrity measured by mean diffusivity (standardized beta=0.16; p=0.02). Associations between SLV and gray matter integrity were strongest for the hippocampus and anterior cingulate gyrus (both ?=0.18) as compared to other regions. Associations of SLV with other neuroimaging markers were not significant. Lower integrity of normal-appearing gray matter may underlie higher SLV in older adults. Our results highlighted the hippocampus and anterior cingulate gyrus, regions involved in memory and executive function. These findings support previous research indicating a role for cognitive function in motor control. Higher SLV may indicate focal neuropathology in those without diagnosed neurologic disease.
Related JoVE Video
Effects of long-term averaging of quantitative blood pressure traits on the detection of genetic associations.
Am. J. Hum. Genet.
PUBLISHED: 03-13-2014
Show Abstract
Hide Abstract
Blood pressure (BP) is a heritable, quantitative trait with intraindividual variability and susceptibility to measurement error. Genetic studies of BP generally use single-visit measurements and thus cannot remove variability occurring over months or years. We leveraged the idea that averaging BP measured across time would improve phenotypic accuracy and thereby increase statistical power to detect genetic associations. We studied systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) averaged over multiple years in 46,629 individuals of European ancestry. We identified 39 trait-variant associations across 19 independent loci (p < 5 × 10(-8)); five associations (in four loci) uniquely identified by our LTA analyses included those of SBP and MAP at 2p23 (rs1275988, near KCNK3), DBP at 2q11.2 (rs7599598, in FER1L5), and PP at 6p21 (rs10948071, near CRIP3) and 7p13 (rs2949837, near IGFBP3). Replication analyses conducted in cohorts with single-visit BP data showed positive replication of associations and a nominal association (p < 0.05). We estimated a 20% gain in statistical power with long-term average (LTA) as compared to single-visit BP association studies. Using LTA analysis, we identified genetic loci influencing BP. LTA might be one way of increasing the power of genetic associations for continuous traits in extant samples for other phenotypes that are measured serially over time.
Related JoVE Video
Serum bicarbonate concentrations and kidney disease progression in community-living elders: the Health, Aging, and Body Composition (Health ABC) Study.
Am. J. Kidney Dis.
PUBLISHED: 03-12-2014
Show Abstract
Hide Abstract
In populations with prevalent chronic kidney disease (CKD), lower serum bicarbonate levels are associated with more rapid CKD progression, but whether lower bicarbonate levels also are associated with risk of incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) and CKD progression among community-living persons with predominantly preserved kidney function is unknown.
Related JoVE Video
Segmental Kidney Volumes Measured by Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Their Association With CKD in Older People.
Am. J. Kidney Dis.
PUBLISHED: 02-28-2014
Show Abstract
Hide Abstract
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a potentially powerful tool for analysis of kidney structure and function. The ability to measure functional and hypofunctional tissues could provide important information in groups at risk for chronic kidney disease (CKD), such as the elderly.
Related JoVE Video
Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
Iris Postmus, Stella Trompet, Harshal A Deshmukh, Michael R Barnes, Xiaohui Li, Helen R Warren, Daniel I Chasman, Kaixin Zhou, Benoit J Arsenault, Louise A Donnelly, Kerri L Wiggins, Christy L Avery, Paula Griffin, QiPing Feng, Kent D Taylor, Guo Li, Daniel S Evans, Albert V Smith, Catherine E de Keyser, Andrew D Johnson, Anton J M de Craen, David J Stott, Brendan M Buckley, Ian Ford, Rudi G J Westendorp, P Eline Slagboom, Naveed Sattar, Patricia B Munroe, Peter Sever, Neil Poulter, Alice Stanton, Denis C Shields, Eoin O'Brien, Sue Shaw-Hawkins, Y-D Ida Chen, Deborah A Nickerson, Joshua D Smith, Marie Pierre Dubé, S Matthijs Boekholdt, G Kees Hovingh, John J P Kastelein, Paul M McKeigue, John Betteridge, Andrew Neil, Paul N Durrington, Alex Doney, Fiona Carr, Andrew Morris, Mark I McCarthy, Leif Groop, Emma Ahlqvist, , Joshua C Bis, Kenneth Rice, Nicholas L Smith, Thomas Lumley, Eric A Whitsel, Til Stürmer, Eric Boerwinkle, Julius S Ngwa, Christopher J O'Donnell, Ramachandran S Vasan, Wei-Qi Wei, Russell A Wilke, Ching-Ti Liu, Fangui Sun, Xiuqing Guo, Susan R Heckbert, Wendy Post, Nona Sotoodehnia, Alice M Arnold, Jeanette M Stafford, Jingzhong Ding, David M Herrington, Stephen B Kritchevsky, Gudny Eiriksdottir, Leonore J Launer, Tamara B Harris, Audrey Y Chu, Franco Giulianini, Jean G MacFadyen, Bryan J Barratt, Fredrik Nyberg, Bruno H Stricker, André G Uitterlinden, Albert Hofman, Fernando Rivadeneira, Valur Emilsson, Oscar H Franco, Paul M Ridker, Vilmundur Gudnason, Yongmei Liu, Joshua C Denny, Christie M Ballantyne, Jerome I Rotter, L Adrienne Cupples, Bruce M Psaty, Colin N A Palmer, Jean-Claude Tardif, Helen M Colhoun, Graham Hitman, Ronald M Krauss, J Wouter Jukema, Mark J Caulfield.
Nat Commun
PUBLISHED: 02-27-2014
Show Abstract
Hide Abstract
Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
Related JoVE Video
Gene-age interactions in blood pressure regulation: a large-scale investigation with the CHARGE, Global BPgen, and ICBP Consortia.
Jeannette Simino, Gang Shi, Joshua C Bis, Daniel I Chasman, Georg B Ehret, Xiangjun Gu, Xiuqing Guo, Shih-Jen Hwang, Eric Sijbrands, Albert V Smith, Germaine C Verwoert, Jennifer L Bragg-Gresham, Gemma Cadby, Peng Chen, Ching-Yu Cheng, Tanguy Corre, Rudolf A de Boer, Anuj Goel, Toby Johnson, Chiea-Chuen Khor, , Carla Lluis-Ganella, Jian'an Luan, Leo-Pekka Lyytikäinen, Ilja M Nolte, Xueling Sim, Siim Sõber, Peter J van der Most, Niek Verweij, Jing Hua Zhao, Najaf Amin, Eric Boerwinkle, Claude Bouchard, Abbas Dehghan, Gudny Eiriksdottir, Roberto Elosua, Oscar H Franco, Christian Gieger, Tamara B Harris, Serge Hercberg, Albert Hofman, Alan L James, Andrew D Johnson, Mika Kähönen, Kay-Tee Khaw, Zoltan Kutalik, Martin G Larson, Lenore J Launer, Guo Li, Jianjun Liu, Kiang Liu, Alanna C Morrison, Gerjan Navis, Rick Twee-Hee Ong, George J Papanicolau, Brenda W Penninx, Bruce M Psaty, Leslie J Raffel, Olli T Raitakari, Kenneth Rice, Fernando Rivadeneira, Lynda M Rose, Serena Sanna, Robert A Scott, David S Siscovick, Ronald P Stolk, André G Uitterlinden, Dhananjay Vaidya, Melanie M van der Klauw, Ramachandran S Vasan, Eranga Nishanthie Vithana, Uwe Völker, Henry Völzke, Hugh Watkins, Terri L Young, Tin Aung, Murielle Bochud, Martin Farrall, Catharina A Hartman, Maris Laan, Edward G Lakatta, Terho Lehtimäki, Ruth J F Loos, Gavin Lucas, Pierre Meneton, Lyle J Palmer, Rainer Rettig, Harold Snieder, E Shyong Tai, Yik-Ying Teo, Pim van der Harst, Nicholas J Wareham, Cisca Wijmenga, Tien Yin Wong, Myriam Fornage, Vilmundur Gudnason, Daniel Levy, Walter Palmas, Paul M Ridker, Jerome I Rotter, Cornelia M van Duijn, Jacqueline C M Witteman, Aravinda Chakravarti, Dabeeru C Rao.
Am. J. Hum. Genet.
PUBLISHED: 02-22-2014
Show Abstract
Hide Abstract
Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p ? 5 × 10(-8)) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the EHBP1L1 (DBP and MAP), CASZ1 (SBP and MAP), and GOSR2 (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The EHBP1L1 locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 × 10(-4)) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations.
Related JoVE Video
Inter-scanner differences in in vivo QCT measurements of the density and strength of the proximal femur remain after correction with anthropomorphic standardization phantoms.
Med Eng Phys
PUBLISHED: 01-24-2014
Show Abstract
Hide Abstract
In multicenter studies and longitudinal studies that use two or more different quantitative computed tomography (QCT) imaging systems, anthropomorphic standardization phantoms (ASPs) are used to correct inter-scanner differences and allow pooling of data. In this study, in vivo imaging of 20 women on two imaging systems was used to evaluate inter-scanner differences in hip integral BMD (iBMD), trabecular BMD (tBMD), cortical BMD (cBMD), femoral neck yield moment (My) and yield force (Fy), and finite-element derived strength of the femur under stance (FEstance) and fall (FEfall) loading. Six different ASPs were used to derive inter-scanner correction equations. Significant (p<0.05) inter-scanner differences were detected in all measurements except My and FEfall, and no ASP-based correction was able to reduce inter-scanner variability to corresponding levels of intra-scanner precision. Inter-scanner variability was considerably higher than intra-scanner precision, even in cases where the mean inter-scanner difference was statistically insignificant. A significant (p<0.01) effect of body size on inter-scanner differences in BMD was detected, demonstrating a need to address the effects of body size on QCT measurements. The results of this study show that significant inter-scanner differences in QCT-based measurements of BMD and bone strength can remain even when using an ASP.
Related JoVE Video
Genome-wide association study identifies common loci influencing circulating glycated hemoglobin (HbA1c) levels in non-diabetic subjects: the Long Life Family Study (LLFS).
Metab. Clin. Exp.
PUBLISHED: 01-11-2014
Show Abstract
Hide Abstract
Glycated hemoglobin (HbA1c) is a stable index of chronic glycemic status and hyperglycemia associated with progressive development of insulin resistance and frank diabetes. It is also associated with premature aging and increased mortality. To uncover novel loci for HbA1c that are associated with healthy aging, we conducted a genome-wide association study (GWAS) using non-diabetic participants in the Long Life Family Study (LLFS), a study with familial clustering of exceptional longevity in the US and Denmark.
Related JoVE Video
The Challenges of Genome-Wide Interaction Studies: Lessons to Learn from the Analysis of HDL Blood Levels.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Genome-wide association studies (GWAS) have revealed 74 single nucleotide polymorphisms (SNPs) associated with high-density lipoprotein cholesterol (HDL) blood levels. This study is, to our knowledge, the first genome-wide interaction study (GWIS) to identify SNP×SNP interactions associated with HDL levels. We performed a GWIS in the Rotterdam Study (RS) cohort I (RS-I) using the GLIDE tool which leverages the massively parallel computing power of Graphics Processing Units (GPUs) to perform linear regression on all genome-wide pairs of SNPs. By performing a meta-analysis together with Rotterdam Study cohorts II and III (RS-II and RS-III), we were able to filter 181 interaction terms with a p-value<1 · 10-8 that replicated in the two independent cohorts. We were not able to replicate any of these interaction term in the AGES, ARIC, CHS, ERF, FHS and NFBC-66 cohorts (Ntotal?=?30,011) when adjusting for multiple testing. Our GWIS resulted in the consistent finding of a possible interaction between rs774801 in ARMC8 (ENSG00000114098) and rs12442098 in SPATA8 (ENSG00000185594) being associated with HDL levels. However, p-values do not reach the preset Bonferroni correction of the p-values. Our study suggest that even for highly genetically determined traits such as HDL the sample sizes needed to detect SNP×SNP interactions are large and the 2-step filtering approaches do not yield a solution. Here we present our analysis plan and our reservations concerning GWIS.
Related JoVE Video
Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.
Related JoVE Video
Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
Valentina Escott-Price, Celine Bellenguez, Li-San Wang, Seung-Hoan Choi, Denise Harold, Lesley Jones, Peter Holmans, Amy Gerrish, Alexey Vedernikov, Alexander Richards, Anita L Destefano, Jean-Charles Lambert, Carla A Ibrahim-Verbaas, Adam C Naj, Rebecca Sims, Gyungah Jun, Joshua C Bis, Gary W Beecham, Benjamin Grenier-Boley, Giancarlo Russo, Tricia A Thornton-Wells, Nicola Denning, Albert V Smith, Vincent Chouraki, Charlene Thomas, M Arfan Ikram, Diana Zelenika, Badri N Vardarajan, Yoichiro Kamatani, Chiao-Feng Lin, Helena Schmidt, Brian Kunkle, Melanie L Dunstan, Maria Vronskaya, , Andrew D Johnson, Agustin Ruíz, Marie-Therese Bihoreau, Christiane Reitz, Florence Pasquier, Paul Hollingworth, Olivier Hanon, Annette L Fitzpatrick, Joseph D Buxbaum, Dominique Campion, Paul K Crane, Clinton Baldwin, Tim Becker, Vilmundur Gudnason, Carlos Cruchaga, David Craig, Najaf Amin, Claudine Berr, Oscar L Lopez, Philip L De Jager, Vincent Deramecourt, Janet A Johnston, Denis Evans, Simon Lovestone, Luc Letenneur, Isabel Hernández, David C Rubinsztein, Gudny Eiriksdottir, Kristel Sleegers, Alison M Goate, Nathalie Fiévet, Matthew J Huentelman, Michael Gill, Kristelle Brown, M Ilyas Kamboh, Lina Keller, Pascale Barberger-Gateau, Bernadette McGuinness, Eric B Larson, Amanda J Myers, Carole Dufouil, Stephen Todd, David Wallon, Seth Love, Ekaterina Rogaeva, John Gallacher, Peter St George-Hyslop, Jordi Clarimón, Alberto Lleó, Anthony Bayer, Debby W Tsuang, Lei Yu, Magda Tsolaki, Paola Bossù, Gianfranco Spalletta, Petra Proitsi, John Collinge, Sandro Sorbi, Florentino Sanchez Garcia, Nick C Fox, John Hardy, Maria Candida Deniz Naranjo, Paolo Bosco, Robert Clarke, Carol Brayne, Daniela Galimberti, Elio Scarpini, Ubaldo Bonuccelli, Michelangelo Mancuso, Gabriele Siciliano, Susanne Moebus, Patrizia Mecocci, Maria Del Zompo, Wolfgang Maier, Harald Hampel, Alberto Pilotto, Ana Frank-García, Francesco Panza, Vincenzo Solfrizzi, Paolo Caffarra, Benedetta Nacmias, William Perry, Manuel Mayhaus, Lars Lannfelt, Hakon Hakonarson, Sabrina Pichler, Minerva M Carrasquillo, Martin Ingelsson, Duane Beekly, Victoria Alvarez, Fanggeng Zou, Otto Valladares, Steven G Younkin, Eliecer Coto, Kara L Hamilton-Nelson, Wei Gu, Cristina Razquin, Pau Pastor, Ignacio Mateo, Michael J Owen, Kelley M Faber, Palmi V Jonsson, Onofre Combarros, Michael C O'Donovan, Laura B Cantwell, Hilkka Soininen, Deborah Blacker, Simon Mead, Thomas H Mosley, David A Bennett, Tamara B Harris, Laura Fratiglioni, Clive Holmes, Renée F A G de Bruijn, Peter Passmore, Thomas J Montine, Karolien Bettens, Jerome I Rotter, Alexis Brice, Kevin Morgan, Tatiana M Foroud, Walter A Kukull, Didier Hannequin, John F Powell, Michael A Nalls, Karen Ritchie, Kathryn L Lunetta, John S K Kauwe, Eric Boerwinkle, Matthias Riemenschneider, Mercè Boada, Mikko Hiltunen, Eden R Martin, Reinhold Schmidt, Dan Rujescu, Jean-Francois Dartigues, Richard Mayeux, Christophe Tzourio, Albert Hofman, Markus M Nöthen, Caroline Graff, Bruce M Psaty, Jonathan L Haines, Mark Lathrop, Margaret A Pericak-Vance, Lenore J Launer, Christine Van Broeckhoven, Lindsay A Farrer, Cornelia M van Duijn, Alfredo Ramírez, Sudha Seshadri, Gerard D Schellenberg, Philippe Amouyel, Julie Williams.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Related JoVE Video
Patterns of leisure-time physical activity participation in a British birth cohort at early old age.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Using data from a nationally representative British birth cohort we characterized the type and diversity of leisure-time physical activity that 2,188 participants (age 60-64 years) engaged in throughout the year by gender and obesity. Participants most commonly reported walking (71%), swimming (33%), floor exercises (24%) and cycling (15%). Sixty-two percent of participants reported ? 2 activities in the past year and 40% reported diversity on a regular basis. Regular engagement in different types of activity (cardio-respiratory, balance/flexibility and strength) was reported by 67%, 19% and 11% of participants, respectively. We found gender differences, as well as differences by obesity status, in the activities reported, the levels of activity diversity and activity type. Non-obese participants had greater activity diversity, and more often reported activities beneficial for cardio-respiratory health and balance/flexibility than obese participants. These findings may be used to inform the development of trials of physical activity interventions targeting older adults, and those older adults with high body mass index.
Related JoVE Video
Effect of socioeconomic disparities on incidence of dementia among biracial older adults: prospective study.
BMJ
PUBLISHED: 12-21-2013
Show Abstract
Hide Abstract
To examine whether observed differences in dementia rates between black and white older people living in the community could be explained by measures of socioeconomic status (income, financial adequacy, education, and literacy) and health related factors.
Related JoVE Video
Body mass and weight change in adults in relation to mortality risk.
Am. J. Epidemiol.
PUBLISHED: 10-29-2013
Show Abstract
Hide Abstract
Using data from the National Institutes of Health-AARP Diet and Health Study, we evaluated the influence of adulthood weight history on mortality risk. The National Institutes of Health-AARP Diet and Health Study is an observational cohort study of US men and women who were aged 50-71 years at entry in 1995-1996. This analysis focused on 109,947 subjects who had never smoked and were younger than age 70 years. We estimated hazard ratios of total and cause-specific mortality for recalled body mass index (BMI; weight (kg)/height (m)(2)) at ages 18, 35, and 50 years; weight change across 3 adult age intervals; and the effect of first attaining an elevated BMI at 4 successive ages. During 12.5 years follow-up through 2009, 12,017 deaths occurred. BMI at all ages was positively related to mortality. Weight gain was positively related to mortality, with stronger associations for gain between ages 18 and 35 years and ages 35 and 50 years than between ages 50 and 69 years. Mortality risks were higher in persons who attained or exceeded a BMI of 25.0 at a younger age than in persons who reached that threshold later in adulthood, and risks were lowest in persons who maintained a BMI below 25.0. Heavier initial BMI and weight gain in early to middle adulthood strongly predicted mortality risk in persons aged 50-69 years.
Related JoVE Video
Association Between Cerebellar Gray Matter Volumes, Gait Speed, and Information-Processing Ability in Older Adults Enrolled in the Health ABC Study.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 10-29-2013
Show Abstract
Hide Abstract
The cerebellum plays an important role in mobility and cognition. However, it is unclear which regions of the cerebellum are associated with gait speed and information-processing ability in older adults without overt brain damage.
Related JoVE Video
Older Adults With Limited Literacy Are at Increased Risk for Likely Dementia.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 10-24-2013
Show Abstract
Hide Abstract
Low literacy is common among the elderly and possibly more reflective of educational attainment than years of school completed. We examined the association between literacy and risk of likely dementia in older adults.
Related JoVE Video
Diabetes and risk of hospitalized fall injury among older adults.
Diabetes Care
PUBLISHED: 10-15-2013
Show Abstract
Hide Abstract
OBJECTIVE To determine whether older adults with diabetes are at increased risk of an injurious fall requiring hospitalization. RESEARCH DESIGN AND METHODS The longitudinal Health, Aging, and Body Composition Study included 3,075 adults aged 70-79 years at baseline. Hospitalizations that included ICD-9-Clinical Modification codes for a fall and an injury were identified. The effect of diabetes with and without insulin use on the rate of first fall-related injury hospitalization was assessed using proportional hazards models. RESULTS At baseline, 719 participants had diabetes, and 117 of them were using insulin. Of the 293 participants who were hospitalized for a fall-related injury, 71 had diabetes, and 16 were using insulin. Diabetes was associated with a higher rate of injurious fall requiring hospitalization (hazard ratio [HR] 1.48 [95% CI 1.12-1.95]) in models adjusted for age, race, sex, BMI, and education. In those participants using insulin, compared with participants without diabetes, the HR was 3.00 (1.78-5.07). Additional adjustment for potential intermediaries, such as fainting in the past year, standing balance score, cystatin C level, and number of prescription medications, accounted for some of the increased risk associated with diabetes (1.41 [1.05-1.88]) and insulin-treated diabetes (2.24 [1.24-4.03]). Among participants with diabetes, a history of falling, poor standing balance score, and A1C level ?8% were risk factors for an injurious fall requiring hospitalization. CONCLUSIONS Older adults with diabetes, in particular those using insulin, are at greater risk of an injurious fall requiring hospitalization than those without diabetes. Among those with diabetes, poor glycemic control may increase the risk of an injurious fall.
Related JoVE Video
Partially ordered mixed hidden Markov model for the disablement process of older adults.
J Am Stat Assoc
PUBLISHED: 09-24-2013
Show Abstract
Hide Abstract
At both the individual and societal levels, the health and economic burden of disability in older adults is enormous in developed countries, including the U.S. Recent studies have revealed that the disablement process in older adults often comprises episodic periods of impaired functioning and periods that are relatively free of disability, amid a secular and natural trend of decline in functioning. Rather than an irreversible, progressive event that is analogous to a chronic disease, disability is better conceptualized and mathematically modeled as states that do not necessarily follow a strict linear order of good-to-bad. Statistical tools, including Markov models, which allow bidirectional transition between states, and random effects models, which allow individual-specific rate of secular decline, are pertinent. In this paper, we propose a mixed effects, multivariate, hidden Markov model to handle partially ordered disability states. The model generalizes the continuation ratio model for ordinal data in the generalized linear model literature and provides a formal framework for testing the effects of risk factors and/or an intervention on the transitions between different disability states. Under a generalization of the proportional odds ratio assumption, the proposed model circumvents the problem of a potentially large number of parameters when the number of states and the number of covariates are substantial. We describe a maximum likelihood method for estimating the partially ordered, mixed effects model and show how the model can be applied to a longitudinal data set that consists of N = 2,903 older adults followed for 10 years in the Health Aging and Body Composition Study. We further statistically test the effects of various risk factors upon the probabilities of transition into various severe disability states. The result can be used to inform geriatric and public health science researchers who study the disablement process.
Related JoVE Video
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
Show Abstract
Hide Abstract
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.
Related JoVE Video
Common variants in mendelian kidney disease genes and their association with renal function.
Afshin Parsa, Christian Fuchsberger, Anna Köttgen, Conall M O'Seaghdha, Cristian Pattaro, Mariza de Andrade, Daniel I Chasman, Alexander Teumer, Karlhans Endlich, Matthias Olden, Ming-Huei Chen, Adrienne Tin, Young J Kim, Daniel Taliun, Man Li, Mary Feitosa, Mathias Gorski, Qiong Yang, Claudia Hundertmark, Meredith C Foster, Nicole Glazer, Aaron Isaacs, Madhumathi Rao, Albert V Smith, Jeffrey R O'Connell, Maksim Struchalin, Toshiko Tanaka, Guo Li, Shih-Jen Hwang, Elizabeth J Atkinson, Kurt Lohman, Marilyn C Cornelis, Asa Johansson, Anke Tönjes, Abbas Dehghan, Vincent Couraki, Elizabeth G Holliday, Rossella Sorice, Zoltan Kutalik, Terho Lehtimäki, Tonu Esko, Harshal Deshmukh, Sheila Ulivi, Audrey Y Chu, Federico Murgia, Stella Trompet, Medea Imboden, Barbara Kollerits, Giorgio Pistis, Tamara B Harris, Lenore J Launer, Thor Aspelund, Gudny Eiriksdottir, Braxton D Mitchell, Eric Boerwinkle, Helena Schmidt, Edith Hofer, Frank Hu, Ayse Demirkan, Ben A Oostra, Stephen T Turner, Jingzhong Ding, Jeanette S Andrews, Barry I Freedman, Franco Giulianini, Wolfgang Koenig, Thomas Illig, Angela Döring, H-Erich Wichmann, Lina Zgaga, Tatijana Zemunik, Mladen Boban, Cosetta Minelli, Heather E Wheeler, Wilmar Igl, Ghazal Zaboli, Sarah H Wild, Alan F Wright, Harry Campbell, David Ellinghaus, Ute Nöthlings, Gunnar Jacobs, Reiner Biffar, Florian Ernst, Georg Homuth, Heyo K Kroemer, Matthias Nauck, Sylvia Stracke, Uwe Völker, Henry Völzke, Peter Kovacs, Michael Stumvoll, Reedik Mägi, Albert Hofman, André G Uitterlinden, Fernando Rivadeneira, Yurii S Aulchenko, Ozren Polašek, Nick Hastie, Veronique Vitart, Catherine Helmer, Jie Jin Wang, Bénédicte Stengel, Daniela Ruggiero, Sven Bergmann, Mika Kähönen, Jorma Viikari, Tiit Nikopensius, Michael Province, Helen Colhoun, Alex Doney, Antonietta Robino, Bernhard K Krämer, Laura Portas, Ian Ford, Brendan M Buckley, Martin Adam, Gian-Andri Thun, Bernhard Paulweber, Margot Haun, Cinzia Sala, Paul Mitchell, Marina Ciullo, Peter Vollenweider, Olli Raitakari, Andres Metspalu, Colin Palmer, Paolo Gasparini, Mario Pirastu, J Wouter Jukema, Nicole M Probst-Hensch, Florian Kronenberg, Daniela Toniolo, Vilmundur Gudnason, Alan R Shuldiner, Josef Coresh, Reinhold Schmidt, Luigi Ferrucci, Cornelia M van Duijn, Ingrid Borecki, Sharon L R Kardia, Yongmei Liu, Gary C Curhan, Igor Rudan, Ulf Gyllensten, James F Wilson, Andre Franke, Peter P Pramstaller, Rainer Rettig, Inga Prokopenko, Jacqueline Witteman, Caroline Hayward, Paul M Ridker, Murielle Bochud, Iris M Heid, David S Siscovick, Caroline S Fox, W Linda Kao, Carsten A Böger.
J. Am. Soc. Nephrol.
PUBLISHED: 09-12-2013
Show Abstract
Hide Abstract
Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
Related JoVE Video
Transition to Sarcopenia and Determinants of Transitions in Older Adults: A Population-Based Study.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 09-07-2013
Show Abstract
Hide Abstract
Diagnostic criteria for sarcopenia from appendicular lean mass (ALM), strength, and performance have been proposed, but little is known regarding the progression of sarcopenia. We examined the time course of sarcopenia and determinants of transitioning toward and away from sarcopenia.
Related JoVE Video
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
Show Abstract
Hide Abstract
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.
Related JoVE Video
Impairments in hearing and vision impact on mortality in older people: the AGES-Reykjavik Study.
Age Ageing
PUBLISHED: 08-30-2013
Show Abstract
Hide Abstract
to examine the relationships between impairments in hearing and vision and mortality from all-causes and cardiovascular disease (CVD) among older people.
Related JoVE Video
Comparison Between Southern Blots and qPCR Analysis of Leukocyte Telomere Length in the Health ABC Study.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 08-14-2013
Show Abstract
Hide Abstract
Only a few studies, primarily limited to small samples, have examined the relationship between leukocyte telomere length (LTL) data generated by Southern blots, expressed in kilobases, versus quantitative PCR data, expressed in the telomere product/a single gene product (T/S). In the present study, we compared LTL data generated by the two methods in 681 elderly participants (50% African Americans, 50% of European origin, 49.2% women, mean age 73.7±2.9 years) in the Health Aging and Body Composition Study. The correlation between the data generated by the two methods was modest (R(2) = .27). Both methods captured the age effect on LTL and the longer LTL in women than in men. However, only the Southern blot method showed a significantly longer LTL in African Americans than in European decent individuals, which might be attributed to the larger measurement error of the quantitative PCR-based method than the Southern blots.
Related JoVE Video
Structural patterns of the proximal femur in relation to age and hip fracture risk in women.
Bone
PUBLISHED: 08-09-2013
Show Abstract
Hide Abstract
Fractures of the proximal femur are the most devastating outcome of osteoporosis. It is generally understood that age-related changes in hip structure confer increased risk, but there have been few explicit comparisons of such changes in healthy subjects to those with hip fracture. In this study, we used quantitative computed tomography and tensor-based morphometry (TBM) to identify three-dimensional internal structural patterns of the proximal femur associated with age and with incident hip fracture. A population-based cohort of 349 women representing a broad age range (21-97years) was included in this study, along with a cohort of 222 older women (mean age 79±7years) with (n=74) and without (n=148) incident hip fracture. Images were spatially normalized to a standardized space, and age- and fracture-specific morphometric features were identified based on statistical maps of shape features described as local changes of bone volume. Morphometric features were visualized as maps of local contractions and expansions, and significance was displayed as Students t-test statistical maps. Significant age-related changes included local expansions of regions low in volumetric bone mineral density (vBMD) and local contractions of regions high in vBMD. Some significant fracture-related features resembled an accentuated aging process, including local expansion of the superior aspect of the trabecular bone compartment in the femoral neck, with contraction of the adjoining cortical bone. However, other features were observed only in the comparison of hip fracture subjects with age-matched controls including focal contractions of the cortical bone at the superior aspect of the femoral neck, the lateral cortical bone just inferior to the greater trochanter, and the anterior intertrochanteric region. Results of this study support the idea that the spatial distribution of morphometric features is relevant to age-related changes in bone and independent to fracture risk. In women, the identification by TBM of fracture-specific morphometric alterations of the proximal femur, in conjunction with vBMD and clinical risk factors, may improve hip fracture prediction.
Related JoVE Video
Genome-wide association of body fat distribution in African ancestry populations suggests new loci.
Ching-Ti Liu, Keri L Monda, Kira C Taylor, Leslie Lange, Ellen W Demerath, Walter Palmas, Mary K Wojczynski, Jaclyn C Ellis, Mara Z Vitolins, Simin Liu, George J Papanicolaou, Marguerite R Irvin, Luting Xue, Paula J Griffin, Michael A Nalls, Adebowale Adeyemo, Jiankang Liu, Guo Li, Edward A Ruiz-Narváez, Wei-Min Chen, Fang Chen, Brian E Henderson, Robert C Millikan, Christine B Ambrosone, Sara S Strom, Xiuqing Guo, Jeanette S Andrews, Yan V Sun, Thomas H Mosley, Lisa R Yanek, Daniel Shriner, Talin Haritunians, Jerome I Rotter, Elizabeth K Speliotes, Megan Smith, Lynn Rosenberg, Josyf Mychaleckyj, Uma Nayak, Ida Spruill, W Timothy Garvey, Curtis Pettaway, Sarah Nyante, Elisa V Bandera, Angela F Britton, Alan B Zonderman, Laura J Rasmussen-Torvik, Yii-Der Ida Chen, Jingzhong Ding, Kurt Lohman, Stephen B Kritchevsky, Wei Zhao, Patricia A Peyser, Sharon L R Kardia, Edmond Kabagambe, Ulrich Broeckel, Guanjie Chen, Jie Zhou, Sylvia Wassertheil-Smoller, Marian L Neuhouser, Evadnie Rampersaud, Bruce Psaty, Charles Kooperberg, JoAnn E Manson, Lewis H Kuller, Heather M Ochs-Balcom, Karen C Johnson, Lara Sucheston, José M Ordovás, Julie R Palmer, Christopher A Haiman, Barbara McKnight, Barbara V Howard, Diane M Becker, Lawrence F Bielak, Yongmei Liu, Matthew A Allison, Struan F A Grant, Gregory L Burke, Sanjay R Patel, Pamela J Schreiner, Ingrid B Borecki, Michele K Evans, Herman Taylor, Michèle M Sale, Virginia Howard, Christopher S Carlson, Charles N Rotimi, Mary Cushman, Tamara B Harris, Alexander P Reiner, L Adrienne Cupples, Kari E North, Caroline S Fox.
PLoS Genet.
PUBLISHED: 08-01-2013
Show Abstract
Hide Abstract
Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0 × 10(-6) were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10(-8) for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10(-8) for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5 × 10(-8); RREB1: p = 5.7 × 10(-8)). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity.
Related JoVE Video
Anemia and risk of dementia in older adults: findings from the Health ABC study.
Neurology
PUBLISHED: 07-31-2013
Show Abstract
Hide Abstract
To determine whether anemia is associated with incident dementia in older adults.
Related JoVE Video
Genetics of coronary artery calcification among African Americans, a meta-analysis.
BMC Med. Genet.
PUBLISHED: 07-18-2013
Show Abstract
Hide Abstract
Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants.
Related JoVE Video

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.