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Find video protocols related to scientific articles indexed in Pubmed.
Genetics of regular exercise and sedentary behaviors.
Twin Res Hum Genet
PUBLISHED: 07-19-2014
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Studies on the determinants of physical activity have traditionally focused on social factors and environmental barriers, but recent research has shown the additional importance of biological factors, including genetic variation. Here we review the major tenets of this research to arrive at three major conclusions: First, individual differences in physical activity traits are significantly influenced by genetic factors, but genetic contribution varies strongly over age, with heritability of leisure time exercise behavior ranging from 27% to 84% and heritability of sedentary behaviors ranging from 9% to 48%. Second, candidate gene approaches based on animal or human QTLs or on biological relevance (e.g., dopaminergic or cannabinoid activity in the brain, or exercise performance influencing muscle physiology) have not yet yielded the necessary evidence to specify the genetic mechanisms underlying the heritability of physical activity traits. Third, there is significant genetic modulation of the beneficial effects of daily physical activity patterns on strength and endurance improvements and on health-related parameters like body mass index. Further increases in our understanding of the genetic determinants of sedentary and exercise behaviors as well as the genetic modulation of their effects on fitness and health will be key to meaningful future intervention on these behaviors.
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Genetic and environmental stability of intelligence in childhood and adolescence.
Twin Res Hum Genet
PUBLISHED: 05-09-2014
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The present study examined the genetic and environmental contributions to the temporal stability of verbal, non-verbal and general intelligence across a developmental period spanning childhood and adolescence (5-18 years). Longitudinal twin data collected in four different studies on a total of 1,748 twins, comprising 4,641 measurement points in total, were analyzed using genetic adaptations of the simplex model. The heterogeneity in the type of instrument used to assess psychometric intelligence across the different subsamples and ages allowed us to address the auxiliary question of how to optimally utilize the existing longitudinal data in the context of gene-finding studies. The results were consistent across domains (verbal, non-verbal and general intelligence), and indicated that phenotypic stability was driven primarily by the high stability of additive genetic factors, that the stability of common environment was moderate, and that the unique environment contributed primarily to change. The cross-subscale stability was consistently low, indicating a small overlap between different domains of intelligence over time. The high stability of additive genetic factors justifies the use of a linear combination of scores across the different ages in the context of gene-finding studies.
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Child care, socio-economic status and problem behavior: a study of gene-environment interaction in young Dutch twins.
Behav. Genet.
PUBLISHED: 04-18-2014
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The influences of formal child care before age 4 on behavioral problems at 3, 5, and 7 years of age were assessed in 18,932 Dutch twins (3,878 attended formal child care). The effect of formal child care was studied on the average level of problem behavior and as moderator of genetic and non-genetic influences, while taking into account effects of sex and parental socio-economic status (SES). There was a small association between attending formal child care and higher externalizing problems, especially when SES was low. Heritability was lower for formal child care and in lower SES conditions. These effects were largest at age 7 and for externalizing problems. In 7 year-old boys and girls, the difference in heritability between the formal child care group of low SES and the home care group of high SES was 30% for externalizing and ~20% for internalizing problems. The decrease in heritability was explained by a larger influence of the environment, rather than by a decrease in genetic variance. These results support a bioecological model in which heritability is lower in circumstances associated with more problem behavior.
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GE covariance through phenotype to environment transmission: an assessment in longitudinal twin data and application to childhood anxiety.
Behav. Genet.
PUBLISHED: 04-15-2014
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We considered identification of phenotype (at occasion t) to environment (at occasion t + 1) transmission in longitudinal model comprising genetic, common and unique environmental simplex models (autoregressions). This type of transmission, which gives rise to genotype-environment covariance, is considered to be important in developmental psychology. Having established identifying constraints, we addressed the issue of statistical power to detect such transmission given a limited set of parameter values. The power is very poor in the ACE simplex, but is good in the AE model. We investigated misspecification, and found that fitting the standard ACE simplex to covariance matrices generated by an AE simplex with phenotype to E transmission produces the particular result of a rank 1 C (common environment) covariance matrix with positive transmission, and a rank 1 D (dominance) matrix given negative transmission. We applied the models to mother ratings of anxiety in female twins (aged 3, 7, 10, and 12 years), and obtained support for the positive effect of one twin's phenotype on the other twin's environment.
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Assessing genetic influences on behavior: informant and context dependency as illustrated by the analysis of attention problems.
Behav. Genet.
PUBLISHED: 04-04-2014
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Assessment of genetic influences on behavior depends on context, informants, and study design: We show (analytically) that, conditional on study design, informant specific genetic variance is included in the genetic variance component or in the environmental variance component. To aid the explanation, we present an illustrative empirical analysis of data from the Netherlands Twin Register. Subjects included 1,571 monozygotic and 2,672 dizygotic 12-year-old twin pairs whose attention problems (AP) were rated by their parents, teachers, and themselves. Heritability estimates (h(2)) of AP were about ~0.75 for same informant ratings (mother, father, and same teacher ratings) and ~0.54 for different informants' ratings (different parents', different teachers', and two twins' self-ratings). Awareness of assessment effects is relevant to research into psychiatric disorders. Differences in assessment can account for age effects, such as a drop in heritability of ADHD symptoms. In genome-wide association studies, effects of rating specific genetic influences will be undetectable.
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The dopaminergic reward system and leisure time exercise behavior: a candidate allele study.
Biomed Res Int
PUBLISHED: 03-09-2014
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Twin studies provide evidence that genetic influences contribute strongly to individual differences in exercise behavior. We hypothesize that part of this heritability is explained by genetic variation in the dopaminergic reward system. Eight single nucleotide polymorphisms (SNPs in DRD1: rs265981, DRD2: rs6275, rs1800497, DRD3: rs6280, DRD4: rs1800955, DBH: rs1611115, rs2519152, and in COMT: rs4680) and three variable number of tandem repeats (VNTRs in DRD4, upstream of DRD5, and in DAT1) were investigated for an association with regular leisure time exercise behavior.
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Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update.
Qual Life Res
PUBLISHED: 02-19-2014
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There is compelling evidence of a genetic foundation of patient-reported quality of life (QOL). Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010.
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Epigenetic variation in monozygotic twins: a genome-wide analysis of DNA methylation in buccal cells.
Genes (Basel)
PUBLISHED: 02-07-2014
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DNA methylation is one of the most extensively studied epigenetic marks in humans. Yet, it is largely unknown what causes variation in DNA methylation between individuals. The comparison of DNA methylation profiles of monozygotic (MZ) twins offers a unique experimental design to examine the extent to which such variation is related to individual-specific environmental influences and stochastic events or to familial factors (DNA sequence and shared environment). We measured genome-wide DNA methylation in buccal samples from ten MZ pairs (age 8-19) using the Illumina 450k array and examined twin correlations for methylation level at 420,921 CpGs after QC. After selecting CpGs showing the most variation in the methylation level between subjects, the mean genome-wide correlation (rho) was 0.54. The correlation was higher, on average, for CpGs within CpG islands (CGIs), compared to CGI shores, shelves and non-CGI regions, particularly at hypomethylated CpGs. This finding suggests that individual-specific environmental and stochastic influences account for more variation in DNA methylation in CpG-poor regions. Our findings also indicate that it is worthwhile to examine heritable and shared environmental influences on buccal DNA methylation in larger studies that also include dizygotic twins.
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Smoking During Adolescence as a Risk Factor for Attention Problems.
Biol. Psychiatry
PUBLISHED: 01-15-2014
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Cigarette smoking and attention-deficit/hyperactivity disorder (ADHD) are highly comorbid. One explanation is that individuals with ADHD use cigarettes as "self-medication" to alleviate their attention problems. However, animal studies reported that exposure to nicotine during adolescence influences the developing brain and negatively affects attention. This is the first human study exploring the effects of smoking during adolescence on attention problems.
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Genetic and environmental influences on individual differences in sleep duration during adolescence.
Twin Res Hum Genet
PUBLISHED: 11-04-2013
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This study assessed to what extent genetic and environmental factors contributed to individual differences in adolescent sleep duration, and whether genetic and environmental contributions to sleep duration changed throughout adolescence. A twin-family design was used to gain insight into the genetic and environmental contributions to variation in sleep duration. The study sample consisted of 6,319 adolescent twins (44% males) and 1,359 non-twin siblings (44% males) in the age range of 12 to 20 years (mean age = 16.85, SD = 1.40). The participants self-reported usual sleep duration, which was categorized as less than 8 hours per night, 8-9 hours per night, and more than 9 hours per night. Results showed that the prevalence of shorter than optimum sleep duration, that is, less than 8 hours per night, was high, with the highest prevalence rates in later adolescence. The contribution of genetic and environmental factors to individual differences in sleep duration was dependent on age. Variation in sleep duration at the age of 12 years was accounted for by genetic (boys: 34%, girls: 36%), shared environmental (boys: 28%, girls: 45%), and non-shared environmental factors (boys: 38%, girls: 19%). At the age of 20 years, the role of genetic (boys: 47%, girls: 33%) and non-shared environmental factors (boys: 53%, girls: 67%) was more pronounced. It can be concluded from the results that individual differences in sleep duration were accounted for by genetic and non-shared environmental factors throughout adolescence, whereas shared environmental factors account for a substantial part of variation during early adolescence only.
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The Predictive Value of Smoking Expectancy and the Heritability of its Accuracy.
Nicotine Tob. Res.
PUBLISHED: 10-29-2013
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In smokers, former smokers, and never-smokers, this study aimed to (a) determine the predictive value of smoking expectancy on future smoking status and (b) test the relative contribution of genes and environment to a persons ability to accurately predict future smoking status. For smokers, smoking expectancy reflects the intention to continue smoking, for former smokers to take up smoking again, and for never-smokers to initiate smoking.
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Association study of the estrogen receptor I gene (ESR1) in anorexia nervosa and eating disorders: No replication found.
Int J Eat Disord
PUBLISHED: 10-01-2013
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The female preponderance and onset around puberty in the majority of eating disorders (EDs) suggest that sex hormones, like estrogens, may be involved in the onset of these disorders. An eight-SNP haplotype at the estrogen receptor I (ESR1) gene was found to be associated with anorexia nervosa (AN) (Versini et al., Neuropsychopharmacology, 35, 1818-1825, 2010) and three SNPs from this haplotype (rs726281, rs2295193, and rs3798577) were associated with AN and/or EDs. Our objective was to replicate these findings in an independent cohort of 520 patients with an eating disorder, of whom 244 had AN (142 restricting type) from the GenED study and 2,810 random women from the Netherlands Twin Registry.
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Association between autozygosity and major depression: stratification due to religious assortment.
Behav. Genet.
PUBLISHED: 06-16-2013
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The effects of inbreeding on the health of offspring can be studied by measuring genome-wide autozygosity as the proportion of the genome in runs of homozygosity (F roh) and relate F roh to outcomes such as psychiatric phenotypes. To successfully conduct these studies, the main patterns of variation for genome-wide autozygosity between and within populations should be well understood and accounted for. Within population variation was investigated in the Dutch population by comparing autozygosity between religious and non-religious groups. The Netherlands have a history of societal segregation and assortment based on religious affiliation, which may have increased parental relatedness within religious groups. Religion has been associated with several psychiatric phenotypes, such as major depressive disorder (MDD). We investigated whether there is an association between autozygosity and MDD, and the extent to which this association can be explained by religious affiliation. All F roh analyses included adjustment for ancestry-informative principal components (PCs) and geographic factors. Religious affiliation was significantly associated with autozygosity, showing that F roh has the ability to capture within population differences that are not captured by ancestry-informative PCs or geographic factors. The non-religious group had significantly lower F roh values and significantly more MDD cases, leading to a nominally significant negative association between autozygosity and depression. After accounting for religious affiliation, MDD was not associated with F roh, indicating that the relation between MDD and inbreeding was due to stratification. This study shows how past religious assortment and recent secularization can have genetic consequences in a relatively small country. This warrants accounting for the historical social context and its effects on genetic variation in association studies on psychiatric and other related traits.
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Molecular genetics and subjective well-being.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-24-2013
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Subjective well-being (SWB) is a major topic of research across the social sciences. Twin and family studies have found that genetic factors may account for as much as 30-40% of the variance in SWB. Here, we study genetic contributions to SWB in a pooled sample of ? 11,500 unrelated, comprehensively-genotyped Swedish and Dutch individuals. We apply a recently developed method to estimate "common narrow heritability": the fraction of variance in SWB that can be explained by the cumulative additive effects of genetic polymorphisms that are common in the population. Our estimates are 5-10% for single-question survey measures of SWB, and 12-18% after correction for measurement error in the SWB measures. Our results suggest guarded optimism about the prospects of using genetic data in SWB research because, although the common narrow heritability is not large, the polymorphisms that contribute to it could feasibly be discovered with a sufficiently large sample of individuals.
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Developmental prediction model for early alcohol initiation in Dutch adolescents.
J Stud Alcohol Drugs
PUBLISHED: 05-15-2013
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Multiple factors predict early alcohol initiation in teenagers. Among these are genetic risk factors, childhood behavioral problems, life events, lifestyle, and family environment. We constructed a developmental prediction model for alcohol initiation below the Dutch legal drinking age (16 years), elaborating on the pathways identified by earlier studies.
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A prospective study of the effects of breastfeeding and FADS2 polymorphisms on cognition and hyperactivity/attention problems.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 05-02-2013
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Breastfeeding has been associated with improved cognitive functioning. There is a beneficial effect on IQ, and possibly on associated phenotypes such as attention problems. It has been suggested that the effect on IQ is moderated by polymorphisms in the FADS2 gene, which is involved in fatty acid metabolism. In this study we tested the relation between breastfeeding and FADS2 polymorphisms on the one hand and IQ, educational attainment, overactivity, and attention problems on the other hand. IQ at age 5, 7, 10, 12, and/or 18 (n = 1,313), educational attainment at age 12 (n = 1,857), overactive behavior at age 3 (n = 2,560), and attention problems assessed at age 7, 10, and 12 years (n = 2,479, n = 2,423, n = 2,226) were predicted by breastfeeding and two SNPs in FADS2 (rs174575 and rs1535). Analyses were performed using structural equation modeling. After correction for maternal education, a main effect of breastfeeding was found for educational attainment at age 12 and overactive behavior at age 3. For IQ, the effect of breastfeeding across age was marginally significant (P = 0.05) and amounted to 1.6 points after correcting for maternal education. Neither a main effect of the FADS2 polymorphisms nor an interaction with breastfeeding was detected for any of the phenotypes. This developmentally informed study confirms that breastfeeding is associated with higher educational attainment at age 12, less overactive behavior at age 3 and a trend toward higher IQ after correction for maternal education. In general, the benefits of breastfeeding were small and did not interact with SNPs in FADS2.
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A Twin-Sibling Study on the Relationship Between Exercise Attitudes and Exercise Behavior.
Behav. Genet.
PUBLISHED: 02-27-2013
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Social cognitive models of health behavior propose that individual differences in leisure time exercise behavior are influenced by the attitudes towards exercise. At the same time, large scale twin-family studies show a significant influence of genetic factors on regular exercise behavior. This twin-sibling study aimed to unite these findings by demonstrating that exercise attitudes can be heritable themselves. Secondly, the genetic and environmental cross-trait correlations and the monozygotic (MZ) twin intrapair differences model were used to test whether the association between exercise attitudes and exercise behavior can be causal. Survey data were obtained from 5,095 twins and siblings (18-50 years). A genetic contribution was found for exercise behavior (50 % in males, 43 % in females) and for the six exercise attitude components derived from principal component analysis: perceived benefits (21, 27 %), lack of skills, support and/or resources (45, 48 %), time constraints (25, 30 %), lack of energy (34, 44 %), lack of enjoyment (47, 44 %), and embarrassment (42, 49 %). These components were predictive of leisure time exercise behavior (R² = 28 %). Bivariate modeling further showed that all the genetic (0.36 < |rA| < 0.80) and all but two unique environmental (0.00 < |rE| < 0.27) correlations between exercise attitudes and exercise behavior were significantly different from zero, which is a necessary condition for the existence of a causal effect driving the association. The correlations between the MZ twins difference scores were in line with this finding. It is concluded that exercise attitudes and exercise behavior are heritable, that attitudes and behavior are partly correlated through pleiotropic genetic effects, but that the data are compatible with a causal association between exercise attitudes and behavior.
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Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.
Hum. Mol. Genet.
PUBLISHED: 02-27-2013
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The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P < 1.67 × 10(-8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.
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Increases in alcohol consumption in women and elderly groups: evidence from an epidemiological study.
BMC Public Health
PUBLISHED: 02-24-2013
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BACKGROUND: In most Western countries, alcohol consumption continues to increase, specifically among women and older adults. Insight into these trends may aid intervention strategies. Here we present data on alcohol consumption by age and sex as well as associations between alcohol use and demographic lifestyle/traits. The data are from a large (N>16,000) population-based Dutch sample, ascertained based on the presence of twins in the family. METHODS: A set of 16 indicators of normative and problematic alcohol use was assessed in participants of the Netherlands Twin Register between 2009--2012 (ages 18--97; 6,052 men; 10,535 women). Alcohol consumption and demographic/lifestyle traits, including educational attainment, work-related/financial stress, urbanization, religiousness, smoking/cannabis initiation, and BMI were described by age and sex. Associations were examined by regressing aspects of alcohol use on age, sex, their interaction, and demographic/lifestyle variables. RESULTS: Age, sex, and initiation of cigarette and cannabis use were the most important predictors of alcohol use. Frequency of alcohol use was lowest between 18--25 years, with 3.2% of men and .6% of women drinking 6--7 times/week, and highest above age 65 years, with 30.6-32.7% of men and 20.2-22.0% of women drinking 6--7 times/week. Women consumed the lowest quantities of alcohol between 25--45 years, with a 5.7-5.9% prevalence of excessive drinking (>14 glasses/week), and the largest quantities between 55--65 years (15.5% excessive drinkers). Age at alcohol initiation, onset of regular drinking, and first alcohol intoxication were lowest between ages 18--25 years and highest above age 65 years. Among older participants, men initiated alcohol use and regular drinking earlier, and had lower age at first intoxication than women, but among young adults, no sex differences were observed. CONCLUSIONS: Alcohol consumption was high in the elderly Dutch population, especially among women. Alcohol initiation, onset of regular drinking, and first alcohol intoxication occur at increasingly younger ages, and the previous gap between men and women in age at alcohol initiation, onset of regular drinking, and first alcohol intoxication has closed almost entirely. Heavy alcohol use was most strongly predicted by older age, sex (male), and initiation of smoking and cannabis use.
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Exploring the association between well-being and psychopathology in adolescents.
Behav. Genet.
PUBLISHED: 02-08-2013
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Promotion of mental well-being and prevention of emotional and behavioral problems are suggested to go hand in hand. The present study examined the association between subjective well-being (SWB) and psychopathology and investigated the etiology of this association in a large population-based cohort study of adolescent twins (n = 9,136) and their non-twin siblings (n = 1,474) aged 12-20 years. Phenotypic, genetic, and environmental correlations between SWB and psychopathology were obtained from multivariate genetic modeling conditional on sex. An SWB factor score was used based on measures of subjective happiness, satisfaction with life, and quality of life. Psychopathology was obtained from all syndrome and broad-band scales of the Dutch version of the ASEBA Youth Self Report. Males reported significantly higher levels of SWB than females. Females reported significantly more internalizing problems while males report significantly higher levels of externalizing behavior. In both sexes, significant negative associations were found between SWB and psychopathology, with the strongest associations seen for SWB and the YSR syndrome scale anxious/depression behavior. The observed associations were primarily explained by genetic correlations while non-shared environmental influences were mainly domain specific. The genetic liability to lower levels of SWB are indicative of a genetic liability to higher levels of psychopathology, suggesting that it might be feasible to screen for emotional and behavioral problems before clear signs are present by screening on indices of subjective well-being.
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Separating the domains of oppositional behavior: comparing latent models of the conners oppositional subscale.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 01-03-2013
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Although oppositional defiant disorder (ODD) is usually considered the mildest of the disruptive behavior disorders, it is a key factor in predicting young adult anxiety and depression and is distinguishable from normal childhood behavior. In an effort to understand possible subsets of oppositional defiant behavior (ODB) that may differentially predict outcome, we used latent class analysis of mother report on the Conners Parent Rating Scales Revised Short Forms (CPRS-R:S).
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Trends in adolescent alcohol use: effects of age, sex and cohort on prevalence and heritability.
Addiction
PUBLISHED: 10-26-2011
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To determine the effect of age, sex and cohort on the prevalence and genetic architecture of adolescent alcohol use (AAU).
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Heritability of problem drinking and the genetic overlap with personality in a general population sample.
Front Genet
PUBLISHED: 08-01-2011
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This study examined the heritability of problem drinking and investigated the phenotypic and genetic relationships between problem drinking and personality. In a sample of 5,870 twins and siblings and 4,420 additional family members from the Netherlands Twin Register. Data on problem drinking (assessed with the AUDIT and CAGE; 12 items) and personality [NEO Five-Factor Inventory (FFI); 60 items] were collected in 2009/2010 by surveys. Confirmatory factor analysis on the AUDIT and CAGE items showed that the items clustered on two separate but highly correlated (r?=?0.74) underlying factors. A higher-order factor was extracted that reflected those aspects of problem drinking that are common to the AUDIT and CAGE, which showed a heritability of 40%. The correlations between problem drinking and the five dimensions of personality were small but significant, ranging from 0.06 for Extraversion to -0.12 for Conscientiousness. All personality dimensions (with broad-sense heritabilities between 32 and 55%, and some evidence for non-additive genetic influences) were genetically correlated with problem drinking. The genetic correlations were small to modest (between |0.12| and |0.41|). Future studies with longitudinal data and DNA polymorphisms are needed to determine the biological mechanisms that underlie the genetic link between problem drinking and personality.
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Comparison of naturally conceived and IVF-DZ twins in the Netherlands Twin Registry: a developmental study.
J Pregnancy
PUBLISHED: 07-14-2011
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In a large set of twin pairs, we compared twins born after IVF to naturally conceived twins with respect to birth characteristics, growth, attainment of motor milestones, and emotional and behavioral problems. Twin families were registered with the Netherlands Twin Register. We included 1534 dizygotic (DZ) twins born after IVF, 5315 naturally conceived (NC) DZ twins, and 1504 control NC DZ twins who were matched to the IVF twins based on maternal age, maternal educational level, smoking during pregnancy, gestational age, and offspring sex. Data were obtained by longitudinal surveys sent to fathers, mothers, and teachers at ages 1, 2, 3, 7, 10, and 12 years. Results showed no differences in growth, in attainment of motor milestones, and in behavioral development between IVF and matched NC twins. It can be concluded that for nearly all aspects, development in IVF and NC children is similar.
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Age moderates non-genetic influences on the initiation of cannabis use: a twin-sibling study in Dutch adolescents and young adults.
Addiction
PUBLISHED: 06-24-2011
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To examine the heritability of cannabis initiation, the influence of a possible twin-specific environment and the influence of age on the effects of genes and environment in Dutch adolescents and young adults.
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Genetic and environmental contributions to self-reported thoughts of self-harm and suicide.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 03-18-2011
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Thoughts of self-harm and suicidal behavior are thought to be influenced by both genetics and environment. Molecular genetic studies are beginning to address the question of which genes may be involved and whether different genes may be expressed in men and women. We examined thoughts of self-harm and suicidal behavior in a large general population twin sample including male and female same- and opposite-sex twins. In this study, data on self-reported thoughts of self-harm and suicide were obtained from self-report questionnaires (Beck Depression Inventory and Youth or Adult Self Report forms) in 6,265 twin pairs (11,008 individuals) aged 11-90 (62% female) from the Netherlands Twin Registry. Liability threshold models were compared including sex and age (linear and quadratic) effects. Models were compared using measures of parsimony to calculate the simplest model to the data. A model with additive genetic and unique environmental contributions fitted the data for both males and females. There were no qualitative sex differences, but the relative contributions differed between men and women. Heritability was higher in women (0.74, 95% CI 0.65-0.81) than men (0.45, 95% CI 0.28-0.61). The remaining variance was accounted for by environmental influence unique to an individual. These results suggest contributions from additive genetic factors to self-reported thoughts of self-harm and suicide and support the continued study of both molecular genetic and individual-specific environmental risk factors.
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Trajectories of CBCL attention problems in childhood.
Eur Child Adolesc Psychiatry
PUBLISHED: 02-14-2011
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The first aim of this study was to identify developmental trajectories of Attention Problems in twins followed from age 6 to 12 years. Second, we investigated whether singletons follow similar trajectories. Maternal longitudinal ratings on the Attention Problems (AP) subscale of the Child Behavior Checklist were obtained for a sample of 12,486 twins from the Netherlands Twin Register and for a general population sample of 1,346 singletons. Trajectories were analyzed by growth mixture modeling in twins, and compared with singletons. Teacher ratings on the AP subscale of the Teachers Report Form were available for 7,179 twins and 1,211 singletons, and were used for cross-sectional mean comparisons at each age. All analyses were conducted for boys and girls separately. We identified three linear trajectories in both boys and girls, i.e., stable low (62-71%), low-increasing (15-18%), and high-decreasing (14-21%). Singletons followed three identical trajectories, with similar class proportions. Teacher ratings yielded no differences in mean levels of Attention Problems between twins and singletons. The development of Attention Problems from age 6 to 12 years can be characterized by stable low, low-increasing, and high-decreasing developmental trajectories. Twins and singletons are comparable with respect to the development of Attention Problems in childhood.
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Stable genetic effects on symptoms of alcohol abuse and dependence from adolescence into early adulthood.
Behav. Genet.
PUBLISHED: 02-03-2011
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Relatively little is known about how genetic influences on alcohol abuse and dependence (AAD) change with age. We examined the change in influence of genetic and environmental factors which explain symptoms of AAD from adolescence into early adulthood. Symptoms of AAD were assessed using the four AAD screening questions of the CAGE inventory. Data were obtained up to six times by self-report questionnaires for 8,398 twins from the Netherlands Twin Register aged between 15 and 32 years. Longitudinal genetic simplex modeling was performed with Mx. Results showed that shared environmental influences were present for age 15-17 (57%) and age 18-20 (18%). Unique environmental influences gained importance over time, contributing 15% of the variance at age 15-17 and 48% at age 30-32. At younger ages, unique environmental influences were largely age-specific, while at later ages, age-specific influences became less important. Genetic influences on AAD symptoms over age could be accounted for by one factor, with the relative influence of this factor differing across ages. Genetic influences increased from 28% at age 15-17 to 58% at age 21-23 and remained high in magnitude thereafter. These results are in line with a developmentally stable hypothesis that predicts that a single set of genetic risk factors acts on symptoms of AAD from adolescence into young adulthood.
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Heritability of head size in Dutch and Australian twin families at ages 0-50 years.
Twin Res Hum Genet
PUBLISHED: 08-17-2010
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We assessed the heritability of head circumference, an approximation of brain size, in twin-sib families of different ages. Data from the youngest participants were collected a few weeks after birth and from the oldest participants around age 50 years. In nearly all age groups the largest part of the variation in head circumference was explained by genetic differences. Heritability estimates were 90% in young infants (4 to 5 months), 85-88% in early childhood, 83-87% in adolescence, 75% in young and mid adulthood. In infants younger than 3 months, heritability was very low or absent. Quantitative sex differences in heritability were observed in 15- and 18-year-olds, but there was no evidence for qualitative sex differences, that is, the same genes were expressed in both males and females. Longitudinal analysis of the data between 5, 7, and 18 years of age showed high genetic stability (.78 > R(G) > .98). These results indicate that head circumference is a highly heritable biometric trait and a valid target for future GWA studies.
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The Netherlands Twin Register biobank: a resource for genetic epidemiological studies.
Twin Res Hum Genet
PUBLISHED: 05-19-2010
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In 2004 the Netherlands Twin Register (NTR) started a large scale biological sample collection in twin families to create a resource for genetic studies on health, lifestyle and personality. Between January 2004 and July 2008, adult participants from NTR research projects were invited into the study. During a home visit between 7:00 and 10:00 am, fasting blood and morning urine samples were collected. Fertile women were bled on day 2-4 of the menstrual cycle, or in their pill-free week. Biological samples were collected for DNA isolation, gene expression studies, creation of cell lines and for biomarker assessment. At the time of blood sampling, additional phenotypic information concerning health, medication use, body composition and smoking was collected. Of the participants contacted, 69% participated. Blood and urine samples were collected in 9,530 participants (63% female, average age 44.4 (SD 15.5) years) from 3,477 families. Lipid profile, glucose, insulin, HbA1c, haematology, CRP, fibrinogen, liver enzymes and creatinine have been assessed. Longitudinal survey data on health, personality and lifestyle are currently available for 90% of all participants. Genome-wide SNP data are available for 3,524 participants, with additional genotyping ongoing. The NTR biobank, combined with the extensive phenotypic information available within the NTR, provides a valuable resource for the study of genetic determinants of individual differences in mental and physical health. It offers opportunities for DNA-based and gene expression studies as well as for future metabolomic and proteomic projects.
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Influence of candidate genes on attention problems in children: a longitudinal study.
Behav. Genet.
PUBLISHED: 05-06-2010
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Attention problems form one of the core characteristics of Attention-Deficit Hyperactive Disorder (ADHD), a multifactorial neurodevelopmental disorder. From twin research it is clear that genes play a considerable role in the etiology and in the stability of ADHD in childhood. Association studies have focused on genes involved in the dopaminergic and serotoninergic systems, but with inconclusive results. This study investigated the effect of 26 Single Nucleotide Polymorphisms (SNPs) in genes encoding for serotonin receptors 2A (HTR2A), Catechol-O-Methyltransferase (COMT), Tryptophane Hydroxylase type 2 (TPH2), and Brain Derived Neurotrophic Factor (BDNF). Attention problems (AP) were assessed by parental report at ages 3, 7, 10, and 12 years in more than 16,000 twin pairs. There were 1148 genotyped children with AP data. We developed a longitudinal framework to test the genetic association effect. Based on all phenotypic data, a longitudinal model was formulated with one latent factor loading on all AP measures over time. The broad heritability for the AP latent factor was 82%, and the latent factor explained around 55% of the total phenotypic variance. The association of SNPs with AP was then modeled at the level of this factor. None of the SNPs showed a significant association with AP. The lowest p-value was found for the rs6265 SNP in the BDNF gene (p = 0.035). Overall, our results suggest no evidence for a role of these genes in childhood AP.
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Heritability of anxious-depressive and withdrawn behavior: age-related changes during adolescence.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 04-23-2010
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To explain the differential course of anxiety and depression in individuals from childhood to adulthood by examining age-related changes in the genetic and environmental etiology of anxious and depressive symptoms.
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Moderation of genetic factors by parental divorce in adolescents evaluations of family functioning and subjective wellbeing.
Twin Res Hum Genet
PUBLISHED: 04-20-2010
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Adolescents evaluations of family functioning may have a significant impact on their subjective well-being and adjustment. The aim of the study was to investigate the degree to which genetic and environmental influences affect variation in evaluations of general family functioning, family conflict, and quality of life and the overlap between them. We assessed whether genetic and environmental influences are moderated by parental divorce by analyzing self-report data from 6,773 adolescent twins and their non-twin siblings. Genetic, shared, and nonshared environmental influences accounted for variation in general family functioning and family conflict, with genetic influences being relatively more important in girls than boys in general family functioning. Genetic and nonshared environmental influences accounted for variation in quality of life, with genetic influences being relatively more important in girls. Evidence was found for interaction between genetic factors and parental divorce: genetic influence on general family functioning was larger in participants from divorced families. The overlap between general family functioning and quality of life, and family conflict and quality of life was accounted for the largest part by genetic effects, with nonshared environmental effects accounting for the remaining part. By examining the data from monozygotic twins, we found evidence for interaction between genotype and nonshared, non-measured, environmental influences on evaluations of general family functioning, family conflict, and quality of life.
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Heritability and genome-wide linkage scan of subjective happiness.
Twin Res Hum Genet
PUBLISHED: 04-20-2010
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Causes of individual differences in happiness, as assessed with the Subjective Happiness Scale, are investigated in a large of sample twins and siblings from the Netherlands Twin Register. Over 12,000 twins and siblings, average age 24.7 years (range 12 to 88), took part in the study. A genetic model with an age by sex design was fitted to the data with structural equation modeling in Mx. The heritability of happiness was estimated at 22% for males and 41% in females. No effect of age was observed. To identify the genomic regions contributing to this heritability, a genome-wide linkage study for happiness was conducted in sibling pairs. A subsample of 1157 offspring from 441 families was genotyped with an average of 371 micro-satellite markers per individual. Phenotype and genotype data were analyzed in MERLIN with multipoint variance component linkage analysis and age and sex as covariates. A linkage signal (logarithm of odds score 2.73, empirical p value 0.095) was obtained at the end of the long arm of chromosome 19 for marker D19S254 at 110 cM. A second suggestive linkage peak was found at the short arm of chromosome 1 (LOD of 2.37) at 153 cM, marker D1S534 (empirical p value of .209). These two regions of interest are not overlapping with the regions found for contrasting phenotypes (such as depression, which is negatively associated with happiness). Further linkage and future association studies are warranted.
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Which patient will feel down, which will be happy? The need to study the genetic disposition of emotional states.
Qual Life Res
PUBLISHED: 04-01-2010
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In quality-of-life (QL) research, the genetic susceptibility of negative and positive emotions is frequently ignored, taken for granted, or treated as noise. The objectives are to describe: (1) the major findings of studies addressing the heritable and environmental causes of variation in negative and positive emotional states and (2) the major biological pathways of and genetic variants involved in these emotional states.
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Genetic epidemiology of attention deficit hyperactivity disorder (ADHD index) in adults.
PLoS ONE
PUBLISHED: 03-10-2010
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In contrast to the large number of studies in children, there is little information on the contribution of genetic factors to Attention Deficit Hyperactivity Disorder (ADHD) in adults.
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Pre-divorce problems in 3-year-olds: a prospective study in boys and girls.
Soc Psychiatry Psychiatr Epidemiol
PUBLISHED: 02-18-2010
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We examined to what extent internalizing and externalizing problems at age 3 preceded and predicted parental divorce, and if divorce and the time lapse since divorce were related to internalizing and externalizing problems at age 12.
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A twin-singleton comparison of developmental trajectories of externalizing and internalizing problems in 6- to 12-year-old children.
Twin Res Hum Genet
PUBLISHED: 02-18-2010
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Research on twin-singleton differences in externalizing and internalizing problems in childhood is largely cross-sectional and yields contrasting results. The goal of this study was to compare developmental trajectories of externalizing and internalizing problems in 6- to 12-year-old twins and singletons. Child Behavior Checklist (CBCL) maternal reports of externalizing and internalizing problems were obtained for a sample of 9651 twins from the Netherlands Twin Register and for a representative general population sample of 1351 singletons. Latent growth modeling was applied to estimate growth curves for twins and singletons. Twin-singleton differences in the intercepts and slopes of the growth curves were examined. The developmental trajectories of externalizing problems showed a linear decrease over time, and were not significantly different for twins and singletons. Internalizing problems seem to develop similarly for twins and singletons up to age 9. After this age twins internalizing symptoms start to decrease in comparison to those of singletons, resulting in less internalizing problems than singletons by the age of 12 years. Our findings confirm the generalizability of twin studies to singleton populations with regard to externalizing problems in middle and late childhood. The generalizability of studies on internalizing problems in early adolescence in twin samples should be addressed with care. Twinship may be a protective factor in the development of internalizing problems during early adolescence.
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Genetic Influences on Individual Differences in Exercise Behavior during Adolescence.
Int J Pediatr
PUBLISHED: 01-25-2010
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The aim of this study was to investigate the degree to which genetic and environmental influences affect variation in adolescent exercise behavior. Data on regular leisure time exercise activities were analyzed in 8,355 adolescent twins, from three-age cohorts (13-14, 15-16, and 17-19 years). Exercise behavior was assessed with survey items about type of regular leisure time exercise, frequency, and duration of the activities. Participants were classified as sedentary, regular exercisers, or vigorous exercisers. The prevalence of moderate exercise behavior declined from age 13 to 19 years with a parallel increase in prevalence of sedentary behavior, whereas the prevalence of vigorous exercise behavior remained constant across age cohorts. Variation in exercise behavior was analyzed with genetic structural equation modeling employing a liability threshold model. Variation was largely accounted for by genetic factors (72% to 85% of the variance was explained by genetic factors), whereas shared environmental factors only accounted for a substantial part of the variation in girls aged 13-14 years (46%). We hypothesize that genetic effects on exercise ability may explain the high heritability of exercise behavior in this phase of life.
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Genetic architecture of verbal abilities in children and adolescents.
Dev Sci
PUBLISHED: 10-21-2009
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The etiology of individual differences in general verbal ability, verbal learning and letter and category fluency were examined in two independent samples of 9- and 18-year-old twin pairs and their siblings. In both age groups, we observed strong familial resemblance for general verbal ability and moderate familial resemblance for verbal learning, letter and category fluency. All familial resemblance was explained by genetic factors. There was significant covariance among the tests, which was stronger in magnitude in the adolescent cohort. The covariance was mainly explained by genetic effects shared by subtests, both in middle childhood and in late adolescence. In addition to a shared set of genes that influenced all phenotypes, there were also genetic influences specific to the different verbal phenotypes.
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Heritability of testis size.
Twin Res Hum Genet
PUBLISHED: 08-06-2009
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Testis size is an important feature of male pubertal development. The genetic and environmental contributions to variation in human testis size have hardly been studied. We estimated the heritability of human testicular size in a group of mono- and dizygotic twins and their non-twin brothers (145 twins and 20 brothers from 95 families). Participants were 18 years old on average and all had reached Tanner development stage 4 or higher. Dizygotic twins and their siblings had a larger mean testis volume than monozygotic twins and their siblings. There was significant familial resemblance, with higher correlations in monozygotic twin pairs (0.59) than in dizygotic twin and sibling pairs (0.34). Heritability was estimated at 59% (95% CI = 37-75%), but a model that excluded genetic influences and attributed all familial resemblance to shared environment, fitted the data only marginally worse. The finding of larger mean testis volume in dizygotic twins may be of interest for future research into the mechanisms underlying dizygotic twinning.
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Body size of twins compared with siblings and the general population: from birth to late adolescence.
J. Pediatr.
PUBLISHED: 06-12-2009
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We examined whether and when differences in body size disappear over time and whether twins attain normal final height and body mass index (BMI).
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The establishment of the GENEQOL consortium to investigate the genetic disposition of patient-reported quality-of-life outcomes.
Twin Res Hum Genet
PUBLISHED: 05-22-2009
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To our knowledge, no comprehensive, interdisciplinary initiatives have been taken to examine the role of genetic variants on patient-reported quality-of-life outcomes. The overall objective of this paper is to describe the establishment of an international and interdisciplinary consortium, the GENEQOL Consortium, which intends to investigate the genetic disposition of patient-reported quality-of-life outcomes. We have identified five primary patient-reported quality-of-life outcomes as initial targets: negative psychological affect, positive psychological affect, self-rated physical health, pain, and fatigue. The first tangible objective of the GENEQOL Consortium is to develop a list of potential biological pathways, genes and genetic variants involved in these quality-of-life outcomes, by reviewing current genetic knowledge. The second objective is to design a research agenda to investigate and validate those genes and genetic variants of patient-reported quality-of-life outcomes, by creating large datasets. During its first meeting, the Consortium has discussed draft summary documents addressing these questions for each patient-reported quality-of-life outcome. A summary of the primary pathways and robust findings of the genetic variants involved is presented here. The research agenda outlines possible research objectives and approaches to examine these and new quality-of-life domains. Intriguing questions arising from this endeavor are discussed. Insight into the genetic versus environmental components of patient-reported quality-of-life outcomes will ultimately allow us to explore new pathways for improving patient care. If we can identify patients who are susceptible to poor quality of life, we will be able to better target specific clinical interventions to enhance their quality of life and treatment outcomes.
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Anesthesia and cognitive performance in children: no evidence for a causal relationship.
Twin Res Hum Genet
PUBLISHED: 05-22-2009
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Recent findings of an association between anesthesia administration in the first three years of life and later learning disabilities have created concerns that anesthesia has neurotoxic effects on synaptogenesis, causing later learning problems. An alternative hypothesis is that those children who are likely to undergo surgery early in life have significant medical problems that are associated with a vulnerability to learning disabilities. These two hypotheses were evaluated in a monozygotic concordant-discordant twin design. Data on anesthesia administration and learning abilities and disabilities were available for 1,143 monozygotic twin pairs (56% female) from the Netherlands Twin Registry. Parents of the twins reported on anesthesia use before age 3 and again between ages 3 and 12 years. Near age 12, educational achievement and cognitive problems were assessed with standardized tests and teacher ratings. Results showed that twins who were exposed to anesthesia before age 3 had significantly lower educational achievement scores and significantly more cognitive problems than twins not exposed to anesthesia. However, there was one important exception: the unexposed co-twin from discordant pairs did not differ from their exposed co-twin. Thus, there is no evidence for a causal relationship between anesthesia administration and later learning-related outcomes in this sample. Rather, there is evidence for early anesthesia being a marker of an individuals vulnerability for later learning problems, regardless of their exposure to anesthesia.
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Attention problems, inhibitory control, and intelligence index overlapping genetic factors: a study in 9-, 12-, and 18-year-old twins.
Neuropsychology
PUBLISHED: 05-06-2009
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It is assumed that attention problems (AP) are related to impaired executive functioning. We investigated the association between AP and inhibitory control and tested to what extent the association was due to genetic factors shared with IQ. Data were available from 3 independent samples of 9-, 12-, and 18-year-old twins and their siblings (1,209 participants). AP were assessed with checklists completed by multiple informants. Inhibitory control was measured with the Stroop Color Word Task (Stroop, 1935), and IQ with the Wechsler Intelligence Scale for Children (Wechsler et al., 2002) or Wechsler Adult Intelligence Scale (Wechsler, 1997). AP and inhibitory control were only correlated in the 12-year-old cohort (r = .18), but appeared non-significant after controlling for IQ. Significant correlations existed between AP and IQ in 9- and 12-year olds (r = -.26/-.34). Inhibitory control and IQ were correlated in all cohorts (r = -.16, -.24 and -.35, respectively). Genetic factors that influenced IQ also influenced inhibitory control. We conclude that the association between AP and inhibitory control as reported in the literature may largely derive from genetic factors that are shared with IQ.
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Born to be happy? The etiology of subjective well-being.
Behav. Genet.
PUBLISHED: 03-18-2009
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Subjective Wellbeing (SWB) can be assessed with distinct measures that have been hypothesized to represent different domains of SWB. The current study assessed SWB with four different measures in a genetically informative sample of adolescent twins and their siblings aged 13-28 years (N = 5,024 subjects from 2,157 families). Multivariate genetic modeling was applied to the data to explore the etiology of individual differences in SWB measures and the association among them. Developmental trends and sex differences were examined for mean levels and the variance-covariance structure. Mean SWB levels were equal in men and women. A small negative effect of age on mean levels of SWB was found. Individual differences in SWB were accounted for by additive and non-additive genetic influences, and non-shared environment. The broad-sense heritabilities were estimated between 40 and 50%. The clustering of the four different measures (quality of life in general, satisfaction with life, quality of life at present, and subjective happiness) was explained by an underlying additive genetic factor and an underlying non-additive genetic factor. The effect of these latent genetic factors on the phenotypes was not moderated by either age or sex.
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A twin study of cognitive costs of low birth weight and catch-up growth.
J. Pediatr.
PUBLISHED: 03-04-2009
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To investigate whether there is an association between catch-up growth and cognitive performance in humans.
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A twin study of the genetics of high cognitive ability selected from 11,000 twin pairs in six studies from four countries.
Behav. Genet.
PUBLISHED: 03-03-2009
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Although much genetic research has addressed normal variation in intelligence, little is known about the etiology of high cognitive abilities. Using data from 11,000 twin pairs (age range = 6-71 years) from the genetics of high cognitive abilities consortium, we investigated the genetic and environmental etiologies of high general cognitive ability (g). Age-appropriate psychometric cognitive tests were administered to the twins and used to create g scores standardized within each study. Liability-threshold model fitting was used to estimate genetic and environmental parameters for the top 15% of the distribution of g. Genetic influence for high g was substantial (0.50, with a 95% confidence interval of 0.41-0.60). Shared environmental influences were moderate (0.28, 0.19-0.37). We conclude that genetic variation contributes substantially to high g in Australia, the Netherlands, the United Kingdom and the United States.
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Frequency of truancy at high school: evidence for genetic and twin specific shared environmental influences.
J Adolesc Health
PUBLISHED: 02-25-2009
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The purpose of this study was to examine the relative influence of genetic and environmental factors on variation in truancy during high school. We examined the significance of genetic and shared and nonshared environmental influences. In addition, we tested for the presence of environmental factors specifically shared by twins, but not by their siblings.
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Borderline personality traits and substance use: genetic factors underlie the association with smoking and ever use of cannabis, but not with high alcohol consumption.
J. Pers. Disord.
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Borderline personality disorder (BPD) and substance use disorders often co-occur. Both disorders are heritable and family studies showed that there are familial factors that increase the risk for BPD as well as substance use/abuse. This is the first study that investigates whether the association of borderline personality traits (BPT) with substance use reflects an underlying genetic vulnerability or nongenetic familial influences. To this end we analyzed data of 5,638 Dutch and Belgian twins aged between 21-50 years from 3,567 families. Significant associations between BPT and high alcohol consumption (r = .192), regular smoking (r = .299), and ever use of cannabis (r = .254) were found. Bivariate genetic analyses showed that the associations of BPT and substance use had different etiologies. For regular smoking and for ever use of cannabis, the correlation with BPT was explained by common genetic factors. Interestingly, for high alcohol consumption and BPT the association was explained by unique environmental factors that influence both traits rather than common genetic factors.
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Sex differences in genetic architecture of complex phenotypes?
PLoS ONE
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We examined sex differences in familial resemblance for a broad range of behavioral, psychiatric and health related phenotypes (122 complex traits) in children and adults. There is a renewed interest in the importance of genotype by sex interaction in, for example, genome-wide association (GWA) studies of complex phenotypes. If different genes play a role across sex, GWA studies should consider the effect of genetic variants separately in men and women, which affects statistical power. Twin and family studies offer an opportunity to compare resemblance between opposite-sex family members to the resemblance between same-sex relatives, thereby presenting a test of quantitative and qualitative sex differences in the genetic architecture of complex traits. We analyzed data on lifestyle, personality, psychiatric disorder, health, growth, development and metabolic traits in dizygotic (DZ) same-sex and opposite-sex twins, as these siblings are perfectly matched for age and prenatal exposures. Sample size varied from slightly over 300 subjects for measures of brain function such as EEG power to over 30,000 subjects for childhood psychopathology and birth weight. For most phenotypes, sample sizes were large, with an average sample size of 9027 individuals. By testing whether the resemblance in DZ opposite-sex pairs is the same as in DZ same-sex pairs, we obtain evidence for genetic qualitative sex-differences in the genetic architecture of complex traits for 4% of phenotypes. We conclude that for most traits that were examined, the current evidence is that same the genes are operating in men and women.
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Genetic variation at the TPH2 gene influences impulsivity in addition to eating disorders.
Behav. Genet.
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Genes are involved in eating disorders (EDs) and self-induced vomiting (SV), a key symptom of different types of EDs. Perfectionism and impulsivity are potential risk factors for EDs. TPH2 (tryptophan hydroxylase 2) SNP rs1473473 was previously associated with anorexia nervosa and EDs characterized by SV. Could perfectionism or impulsivity be underlying the association between rs1473473 and EDs? Genetic association between TPH2 SNP rs1473473 and perfectionism or impulsivity was first evaluated in a random control group (N = 512). The associations obtained in this control group were subsequently tested in a group of patients with an ED (N = 267). The minor allele of rs1473473 (OR = 1.49) was more frequent in impulsive controls, but also in impulsive patients with an ED (OR = 1.83). The largest effect was found in the patients with an ED characterized by SV (OR = 2.51, p = 0.02). Genetic variation at the TPH2 gene appeared to affect impulsivity which, in turn, might predispose to the SV phenotype.
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The Young Netherlands Twin Register (YNTR): longitudinal twin and family studies in over 70,000 children.
Twin Res Hum Genet
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The Netherlands Twin Register (NTR) began in 1987 with data collection in twins and their families, including families with newborn twins and triplets. Twenty-five years later, the NTR has collected at least one survey for 70,784 children, born after 1985. For the majority of twins, longitudinal data collection has been done by age-specific surveys. Shortly after giving birth, mothers receive a first survey with items on pregnancy and birth. At age 2, a survey on growth and achievement of milestones is sent. At ages 3, 7, 9/10, and 12 parents and teachers receive a series of surveys that are targeted at the development of emotional and behavior problems. From age 14 years onward, adolescent twins and their siblings report on their behavior problems, health, and lifestyle. When the twins are 18 years and older, parents are also invited to take part in survey studies. In sub-groups of different ages, in-depth phenotyping was done for IQ, electroencephalography , MRI, growth, hormones, neuropsychological assessments, and cardiovascular measures. DNA and biological samples have also been collected and large numbers of twin pairs and parents have been genotyped for zygosity by either micro-satellites or sets of short nucleotide polymorphisms and repeat polymorphisms in candidate genes. Subject recruitment and data collection is still ongoing and the longitudinal database is growing. Data collection by record linkage in the Netherlands is beginning and we expect these combined longitudinal data to provide increased insights into the genetic etiology of development of mental and physical health in children and adolescents.
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Biological pathways and genetic mechanisms involved in social functioning.
Qual Life Res
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To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research.
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Twins, tissue, and time: an assessment of SNPs and CNVs.
Twin Res Hum Genet
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With the desire to assess genetic variation across the lifespan in large-scale collaborative projects, one question is whether inference of copy number (CN) is sensitive to the source of material for deoxyribonucleic acid (DNA) analysis (e.g., blood and buccal) and another question is whether CN is stable as individual sage. Here, we address these questions by applying Affymetrix 6.0 single nucleotide polymorphism (SNP)micro-arrays to 1,472 DNA samples from 710 individuals from the Netherlands Twin Register, including twin and non-twin individuals (372 with buccal and blood derived DNA and 388 with longitudinal data).Similar concordance for CN and genotype inference between samples from the same individual [or from the monozygotic (MZ) co-twins] was found for blood and buccal tissues. There was a small but statistically significant decrease in across-tissue concordance compared with concordance of samples from the same tissue type. No temporal effect was seen on CN variation from the 388 individuals sampled at two time points ranging from 1 to 12 years apart. The majority of our individuals were sampled at age younger than 20 years. Genotype concordance was very high (~ > 99%) between co-twins from 43 MZ pairs. For75 dizygotic (DZ) pairs, ~was ~65%. CN estimates were highly consistent between co-twins from MZ pairs for both deletions (f?2 ~ 90%) and duplications (~ ~ 86%). For DZ, these were similar for within-individual comparisons, but naturally lower between co-twins (~ ~ 50-60%). These results suggest that DNA from buccal samples perform as well as DNA from blood samples on the current generation of micro-array technologies.
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Effect of shared environmental factors on exercise behavior from age 7 to 12 years.
Med Sci Sports Exerc
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The aim of this study was to investigate the relative influence of genetic and environmental factors on childrens leisure time exercise behavior through the classic twin design.
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De novo and inherited CNVs in MZ twin pairs selected for discordance and concordance on Attention Problems.
Eur. J. Hum. Genet.
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Copy number variations (CNVs) have been reported to be causal suspects in a variety of psychopathologic traits. We investigate whether de novo and/or inherited CNVs contribute to the risk for Attention Problems (APs) in children. Based on longitudinal phenotyping, 50 concordant and discordant monozygotic (MZ) twin pairs were selected from a sample of ?3200 MZ pairs. Two types of de novo CNVs were investigated: (1) CNVs shared by both MZ twins, but not inherited (pre-twinning de novo CNVs), which were detected by comparing copy number (CN) calls between parents and twins and (2) CNVs not shared by co-twins (post-twinning de novo CNVs), which were investigated by comparing the CN calls within MZ pairs. The association between the overall CNV burden and AP was also investigated for CNVs genome-wide, CNVs within genes and CNVs outside of genes. Two de novo CNVs were identified and validated using quantitative PCR: a pre-twinning de novo duplication in a concordant-unaffected twin pair and a post-twinning deletion in the higher scoring twin from a concordant-affected pair. For the overall CNV burden analyses, affected individuals had significantly larger CNVs that overlapped with genes than unaffected individuals (P=0.008). This study suggests that the presence of larger CNVs may increase the risk for AP, because they are more likely to affect genes, and confirms that MZ twins are not always genetically identical.
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Genetic and environmental influences on individual differences in sedentary behavior during adolescence: a twin-family study.
Arch Pediatr Adolesc Med
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To investigate the degree to which genetic and environmental influences affect individual differences in sedentary behavior throughout adolescence.
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Regular exercise, subjective wellbeing, and internalizing problems in adolescence: causality or genetic pleiotropy?
Front Genet
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This study tests in a genetically informative design whether exercise behavior causally influences subjective wellbeing (SWB) and internalizing problems (INT). If exercise causally influences SWB and INT, genetic and environmental factors influencing exercise behavior will also influence SWB and INT. Furthermore, within genetically identical (MZ) twin pairs, the twin who exercises more should also show higher levels of SWB and lower levels of INT, than the co-twin who exercises less, because genetic confounding is excluded. Data on these phenotypes were available in a sample of 6317 adolescent twins and 1180 non-twin-siblings. Most participants had longitudinal data with 2-year follow-up. Exercise behavior was cross-sectionally and longitudinally associated with fewer internalizing problems and increased SWB (correlations ranged from 0.12 to 0.16). Cross-sectional and longitudinal associations were mainly accounted for by genetic factors, whereas the contribution of environmental factors was negligible. Within MZ twin pairs, the twin who exercised more did not show fewer internalizing problems and increased SWB. This was found cross-sectionally and longitudinally. We conclude that exercise behavior is associated with fewer internalizing problems and higher levels of SWB. The association largely reflects the effects of common genetic factors on these traits.
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Childhood problem behavior and parental divorce: evidence for gene-environment interaction.
Soc Psychiatry Psychiatr Epidemiol
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The importance of genetic and environmental influences on childrens behavioral and emotional problems may vary as a function of environmental exposure. We previously reported that 12-year-olds with divorced parents showed more internalizing and externalizing problems than children with married parents, and that externalizing problems in girls precede and predict later parental divorce. The aim of the current study was to investigate as to whether genetic and environmental influences on internalizing and externalizing problems were different for children from divorced versus non-divorced families.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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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.