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Although a comparison of concordance rates for deviant scores in identical and fraternal twin pairs can provide prima facie evidence for a genetic etiology, information is not fully utilized when continuous measures are analyzed in a... more
Although a comparison of concordance rates for deviant scores in identical and fraternal twin pairs can provide prima facie evidence for a genetic etiology, information is not fully utilized when continuous measures are analyzed in a dichotomous manner. Thus, DeFries and Fulker (Behav Genet 15:467–473, 1985; Acta Genet Med Gemellol, 37:205–216, 1988) developed a regression-based methodology (DF analysis) to assess genetic etiology in both selected and unselected twin samples. While the DF analysis is a very versatile and relatively powerful statistical approach, it is not easily extended to the multivariate case. In contrast, structural equation models may be readily extended to analyze multivariate data sets (Neale and Cardon, Methodology for genetic studies of twins and families, 1992). However, such methodologies may yield biased estimates of additive genetic, shared environmental, and non-shared environmental influences when multivari-ate models are fitted to selected twin data. Therefore, the Pearson–Aitken (PA) selection formula (Aitken, Proc Edinburgh Math Soc B, 4:106–110, 1934) was used to analyze reading performance data from twins with reading difficulties (selected sample) and a population of normally-achieving twin pairs (control sample). As a comparison, DF models were also fitted to these same data sets. In general, resulting estimates of additive genetic, shared environmental , and non-shared environmental influences were similar when the DF and PA models were fitted to the data. However, the PA selection formula may be more readily generalized to the multivariate case.
Although cross-sectional twin studies have assessed the genetic and environmental etiologies of substance use during adolescence and early adulthood, comparisons of results across different samples, measures, and cohorts are problematic.... more
Although cross-sectional twin studies have assessed the genetic and environmental etiologies of substance use during adolescence and early adulthood, comparisons of results across different samples, measures, and cohorts are problematic. While several longitudinal twin studies have investigated these issues, few corroborating adoption studies have been conducted. The current study is the first to estimate the magnitude of genetic, shared environmental, and non-shared environmental influences on substance use (cigarettes, alcohol, and marijuana) from ages 14 to 18 years, using a prospective longitudinal adoption design. Adoptive and control sibling correlations provided substantial evidence for early genetic effects on cigarette, alcohol, and marijuana use/no use. Shared environmental effects were relatively modest, except for alcohol use, which showed increases in late adolescence (age 17 to 18 years). Sibling similarity for quantity/frequency of use also support additive genetic influences across adolescence, with some shared environmental influences for all three substances. To test the stability of these influences across time, a series of independent pathway models were run to explore common and age-specific influences. For all substances, there were minimal age-specific additive genetic and shared environmental influences on quantity/frequency of use. Further, there was a trend toward increasing genetic influences on cigarette and alcohol use across ages. Genetic influences on marijuana were important early, but did not contribute substantially at age 17 and 18 years. Overall, the findings indicate that genetic influences make important contributions to the frequency/quantity of substance use in adolescence, and suggest that new genetic influences may emerge in late adolescence for cigarette and alcohol use.
The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has... more
The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day…
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Although stressful life events during adolescence are associated with the adoption of unhealthy behaviors such as smoking, both social circumstances and physical traits can moderate the relationship. This study builds on the stress... more
Although stressful life events during adolescence are associated with the adoption of unhealthy behaviors such as smoking, both social circumstances and physical traits can moderate the relationship. This study builds on the stress paradigm and gene-environment approach to social behavior by examining how a polymorphism in the serotonin transporter gene 5-HTTLPR moderates the effect of life events on adolescent smoking. Tests of interaction hypotheses use data from the Family Transitions Project, a longitudinal study of 7th graders followed for 5years. A sibling-pair design with separate models for the gender composition of pairs (brothers, sisters, or brother/sister) controls for unmeasured family background. The results show that negative life events are significantly and positively associated with smoking. Among brother pairs but not other pairs, the results provide evidence of gene-environment interaction by showing that life events more strongly influence smoking behavior for those with more copies of the 5-HTTLPR S allele.
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The early onset of alcohol and tobacco use has been associated with increased risk for later substance abuse and dependence problems. This study investigated genetic and environmental influences on age at onset of alcohol and tobacco use... more
The early onset of alcohol and tobacco use has been associated with increased risk for later substance abuse and dependence problems. This study investigated genetic and environmental influences on age at onset of alcohol and tobacco use by examining twin resemblance for several retrospectively reported onset milestones including age at first use, age at first alcohol intoxication experience, and age at regular use. In addition, we also examined the latency between age at first use and age at regular use of tobacco and alcohol. The subjects were a volunteer sample of older adult twins 50 to 96 years of age. MZ twin correlations for age at first alcohol use and age at first tobacco use were .57 and .44, respectively, compared to .45 and .37 for DZ same-sex twins. MZ twins correlated .30 and .26 for the latencies between first use and regular use of alcohol and of tobacco, while DZ correlations were -.01 and .05, respectively. Biometrical model-fitting results confirmed that familial ...
Research Interests: Genetics, Psychology, Behavior Genetics, Tobacco, Adolescent, and 19 moreHumans, Substance Abuse, Substance Use, Smoking, Tobacco Use, Alcoholism, Female, Alcohol Drinking, Male, Social Environment, Aged, Middle Aged, Adult, Age Factors, Twin Study, Older Adult, Alcohol Use, Neurosciences, and Age at Onset
Using the twin pairs sample from the National Longitudinal Study ofAdolescent Health, we estimate bivariate Cholesky models for the influence of stressful life events (SLEs) on depressive symptoms. We show that depressive symptoms... more
Using the twin pairs sample from the National Longitudinal Study ofAdolescent Health, we estimate bivariate Cholesky models for the influence of stressful life events (SLEs) on depressive symptoms. We show that depressive symptoms (h2Depression = .28) and dependent SLEs (events influenced by an individual's behavior) are both moderately heritable (h2SLE Dependent = .43). We find no evidence for the heritability of independent SLEs. Results from the bivariate Cholesky model suggest that roughly one-half of the correlation between depression and dependent SLEs is due to common genetic factors. Our findings suggest that attempts to characterize the causal effect of SLEs on mental health should limit their list of SLEs to those that are outside of the control of the individual.
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Research Interests: Young Adulthood, Tobacco, Risk assessment, Adolescent, Drug Use, and 24 moreHumans, Substance Use, Smoking, Alcoholism, Female, Alcohol Drinking, Male, Gender Difference, Young Adult, Gender Gap, Risk factors, Ethnic Groups, Longitudinal Studies, IRT-likelihood Ratio, Sex Factors, Odds ratio, Longitudinal data, Age Factors, Risk Factors, Risk Assessment, Alcohol Use, Substance-Related Disorders, Substance Use Disorder, and Marijuana abuse
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Research Interests: Genetics, Psychology, Genetic Drift, Behavior Genetics, Low Dose, and 12 moreMice, Alcoholism, Female, Animals, Male, Ethanol, Sleep, Phenotype, Arousal, Genotype, Neurosciences, and Motor activity
... and Its Relationship to Personality Dimensions, Conduct Disorder, and Substance Use Angela Bryan 1 and Michael C. Stallings 2 Received December 28, 2000; revised December 5, 2001; accepted December 6, 2001 ... 388 Bryan and Stallings... more
... and Its Relationship to Personality Dimensions, Conduct Disorder, and Substance Use Angela Bryan 1 and Michael C. Stallings 2 Received December 28, 2000; revised December 5, 2001; accepted December 6, 2001 ... 388 Bryan and Stallings ...
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In this study we examined the genetic and environmental structure of four dimensions from... more
In this study we examined the genetic and environmental structure of four dimensions from Cloninger's personality system: novelty-seeking (NS), harm-avoidance (HA), reward-dependence (RD), and persistence (PS). Although adult twin studies suggest that these personality dimensions are moderately heritable, this is the first twin study of Cloninger's personality dimensions in adolescence--a period marked by significant physiological and social changes. Study participants included 1851 adolescent twins between the ages of 11 and 18 years; 878 complete twin pairs and 95 singleton-responding twins. Subjects were participants in two community-based samples of twins residing in the state of Colorado. Results indicated that cross-sectional mean levels for NS, HA and RD tended to show modest increases across the adolescent years, while PS showed modest mean decreases. Consistent sex differences in means were found only for RD. Univariate biometrical twin models were used to decompose trait variance into genetic and environmental sources. Results indicated that for NS, HA and RD additive genetic influences and unique environmental effects were sufficient to explain the data. PS, however, could be explained by unique and common environmental effects only, with different patterns of common environmental effects for males and females. We found moderate heritability estimates for NS, HA and RD ranging from .28 to .36--with no evidence for sex-limitation in those influences.
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Research Interests: Marketing, Genetics, Psychology, Cognitive Science, Personality, and 15 moreTwins, Higher Order Thinking, Humans, Personality Assessment Inventory, Female, Male, Temperament, Phenotype, Dimensional, Aged, Journal of Personality and Social Psychology, Middle Aged, Questionnaires, Five Factor Model, and Environment
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Childhood internalizing problems are often precursors in the development of more serious psychiatric syndromes including anxiety and depressive disorders. Twin studies of the etiology of these disorders suggest that the genetic risk... more
Childhood internalizing problems are often precursors in the development of more serious psychiatric syndromes including anxiety and depressive disorders. Twin studies of the etiology of these disorders suggest that the genetic risk factors underlying anxiety and depression are highly correlated. However, the specific genetic mechanisms responsible for this risk have not yet been identified. We examined the association between childhood internalizing problems and a functional polymorphism in the serotonin transporter gene (5-HTTLPR) in 711 children participating in a longitudinal twin study of behavioral and emotional development. Internalizing problems were measured at ages 4, 7, 9, 10, 11 and 12 years using the Child Behavior Checklist (CBCL) parent report form. We applied a sibling-based methodology for estimating allelic association with quantitative traits, while controlling for population stratification. No associations were found for CBCL Internalizing problems at any age, including the subscales for Somatic Complaints, Withdrawn and Anxiety/Depression. Thus, although our results did not support the hypothesis that the 5-HTTLPR contributes to a dimensional expression of internalizing behavior problems, this does not rule out the possibility that it is an interesting polymorphism to pursue in the search for genetic risk factors related to major depressive and/or anxiety disorders.
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We used variable threshold models which accounted for age and gender differences to investigate the genetic and environmental influences on DSM-IV conduct disorder (CD) at the level of symptoms, aggressive versus non-aggressive domains,... more
We used variable threshold models which accounted for age and gender differences to investigate the genetic and environmental influences on DSM-IV conduct disorder (CD) at the level of symptoms, aggressive versus non-aggressive domains, and full-scale. A community sample of 1100 twin pairs (age 11-18) was interviewed using the Diagnostic Interview Schedule for Children. Behavior genetic model fitting suggested that genetic and environmental influences on individual symptoms varied by symptom. The best-fitting models for aggressive and non-aggressive domains, and full-scale CD included additive genetic effects and unique environmental effects only (AE models). These effects could be constrained across age cohorts and sex. The results suggest that using models that incorporate age- and gender-appropriate thresholds specific to each subject we can account for prevalence differences between cohorts. Heritability estimates were .49, .55 and .53 for the aggressive domain, non-aggressive domain, and full-scales, respectively. These results are in contrast to previous research on antisocial behavior measured with the CBCL reporting higher heritability for aggressive versus non-aggressive domains. Results suggest that individual symptoms of CD may be differentially heritable. Additionally, CD assessed using DSM-IV criteria may show differing patterns of heritability compared with estimates obtained for other measures of antisocial behavior such as the CBCL.
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Many putative environmental risks correlate with... more
Many putative environmental risks correlate with individuals' genotypes. The association between delinquent peer affiliation and conduct problems may occur because of shared genetic liability. Five hundred fifty three monozygotic and 558 dizygotic twin pairs, aged 11 to 18 years, were assessed for delinquent peer affiliation and conduct problems. The authors investigated whether genes contribute to both delinquent peer affiliation and the correlation between delinquent peer affiliations and conduct problems. Delinquent peer affiliation was influenced by genetic, shared environmental, and nonshared environmental factors; genetic factors also contributed to the correlation between delinquent peer affiliations and conduct problems, providing evidence for genotype-environment correlation. The magnitude of the genetic variance of conduct problems was contextually dependent on levels of delinquent peer affiliation and was greater at higher levels of delinquent peer affiliation.