Biomedical subjects

Lindon Eaves

Publications and source records attributed to Lindon Eaves.

9 recordsLinked to original sources

PubMed2005

Application of Bayesian inference using Gibbs sampling to item-response theory modeling of multi-symptom genetic data.

Several "genetic" item-response theory (IRT) models are fitted to the responses of 1086 adolescent female twins to the 33 multi-category item Mood and Feeling Questionnaire relating to depressive symptomatology in adolescence. A Markov-chain Monte Carlo (MCMC) algorithm is used within a Bayesian framework for inference using Gibbs sampling, implemented in the program WinBUGS 1.4. The final model incorporated separate genetic and non-shared environmental traits ("A and E") and item-specific genetic effects. Simpler models gave markedly poorer fit to the observations judged by the deviance information criterion (DIC). The common genetic factor showed major loadings on melancholic items, while the environmental factor loaded most highly on items relating to self-deprecation. The MCMC approach provides a convenient and flexible alternative to Maximum Likelihood for estimating the parameters of IRT models for relatively large numbers of items in a genetic context. Additional benefits of the IRT approach are discussed including the estimation of latent trait scores, including genetic factor scores, and their sampling errors.

Adolescent↗

PubMed2004

A twin study of sexual behavior in men.

The role of genetic and environmental influences on age of initiation of first sexual relations and engaging in sexual activity with multiple partners (10 or more partners in 1 year) was investigated in male twins (N = 6,744) from the Vietnam Era Twin Registry. Individual differences in both types of sexual behaviors were heritable, but only age of onset of sexual relations was significantly influenced by the environment shared by the twins. There was a moderate negative correlation between age of initiation of sexual relations and the multiple partners variable; initiating sexual relations earlier was associated with a higher probability of having multiple partners. The additive genetic influence on age of initiation also influenced the multiple partners variable. The substantial unique environmental influences on each variable were uncorrelated with each other. The data suggest that the observed association between age of initiation of sexual relations and having multiple partners is due to genetic influences common to both behaviors.

Adult↗

PubMed2004

Informant disagreement for separation anxiety disorder.

OBJECTIVE: To characterize informant disagreement for separation anxiety disorder (SAD). METHOD: The sample comprised 2,779 8- to 17-year-old twins from a community-based registry. Children and their parents completed a personal interview about the child's psychiatric history. Parents completed a personal interview about their own psychiatric history and a questionnaire about their marital relationship. RESULTS: Informant agreement for SAD ranged between chance and extremely poor. Most cases of SAD were diagnosed by interview with only one informant. SAD diagnosed only by child interview was associated with an increased odds of father-rated oppositional defiant disorder, and vice versa. SAD diagnosed only by parent interview was predicted by the parental informant's history of antisocial personality disorder. SAD diagnosed only by paternal interview was also predicted by mother-rated marital conflict and dissatisfaction. CONCLUSIONS: Parents and children rarely agree about the presence of any level of child separation anxiety. A symptom "or-rule" mostly indexes diagnoses based on interview with only one informant, but the relative validity of such diagnoses remains unclear.

Adolescent↗

PubMed2004

Genetic and environmental influences on the relative timing of pubertal change.

A multicategory item-response theory model was developed to characterize developmental changes in three items relating to the assessment of puberty in adolescent twin girls and boys. The model allowed for the fixed effects of age on probability of endorsing the responses and for the random effects of individual differences on the timing of pubertal changes relative to chronological age. In girls, the model was applied three-wave data on twin pairs (N = 414 female monozygotic [MZ] and 197 female dizygotic [DZ] pairs) and female twins from boy-girl pairs (N = 300 twins) from the Virginia Twin Study of Adolescent Behavioral Development. In boys, the data comprised 318 MZ and 185 DZ pairs and 297 male twins from boy-girl pairs. A total of 3172 and 2790 individual twin assessments were available in girls and boys, respectively, spanning ages 8-17 years. The availability of twin data allows the contributions of genes, the shared environment and individual unique environmental experiences to be resolved in the relative timing of pubertal changes. Parameters of the mixed model including fixed effects of age and random effects of genes and environment were estimated by Markov Chain Monte Carlo simulations using the BUGS algorithm for Gibbs sampling. The estimated standard deviation of random differences in the timing of puberty relative to age was 0.96 years in girls and 1.01 years in boys. The estimated intraclass correlations for the relative timing of pubertal changes were 0.99 +/-0.01 in MZ girls, 0.52 +/-0.02 in DZ girls, 0.88 +/-0.04 in MZ boys and 0.44+/-0.02 in DZ boys, indicating a very large contribution of genetic factors to the relative timing of pubertal change in both sexes. Additive genetic factors account for an estimated 96.3+/-3.3% of the total variance in random effects in girls and 88.0+/-3.6% in boys. Shared environmental influences account for 3.6+/-3.4% in girls and 0% in boys. In girls, nonshared environmental effects explain 0.1+/-0.1% of the total residual variance. The comparable figure in boys is 12.0+/-3.6%.

Adolescent↗

PubMed2003

Markov Chain Monte Carlo approaches to analysis of genetic and environmental components of human developmental change and G x E interaction.

The linear structural model has provided the statistical backbone of the analysis of twin and family data for 25 years. A new generation of questions cannot easily be forced into the framework of current approaches to modeling and data analysis because they involve nonlinear processes. Maximizing the likelihood with respect to parameters of such nonlinear models is often cumbersome and does not yield easily to current numerical methods. The application of Markov Chain Monte Carlo (MCMC) methods to modeling the nonlinear effects of genes and environment in MZ and DZ twins is outlined. Nonlinear developmental change and genotype x environment interaction in the presence of genotype-environment correlation are explored in simulated twin data. The MCMC method recovers the simulated parameters and provides estimates of error and latent (missing) trait values. Possible limitations of MCMC methods are discussed. Further studies are necessary explore the value of an approach that could extend the horizons of research in developmental genetic epidemiology.

Child↗

PubMed2003

Genetic and environmental risk factors in adolescent substance use.

BACKGROUND: The present study was undertaken with the goal of understanding the causes of association between substance use and both conduct disturbance (CD) and depression in adolescent boys and girls. METHOD: Multivariate genetic structural equation models were fitted to multi-informant, multi-wave, longitudinal data collected in extensive home interviews with parents and children with respect to 307 MZ male, 392 MZ female, 185 DZ male, and 187 DZ female, same-sex twin pairs aged 12-17 years from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD). RESULTS: Although conduct disturbance and depression were moderately associated with substance use, the pattern of genetic and environmental risk differed for males and females and across the two disorders. Genetic factors were predominant in girls' substance use whereas boys' use was mediated primarily by shared environmental factors reflecting family dysfunction and deviant peers. The patterns of correlations across the two waves of the study were consistent with conduct disturbance leading to substance use in both males and females, but depression leading to smoking, drug use and, to a lesser extent, alcohol use in girls. CONCLUSIONS: The comorbidity between substance use and depression, and between substance use and conduct disturbance in childhood/adolescence, probably reflects rather different mediating mechanisms--as well as a different time frame, with conduct disturbance preceding substance use but depression following it. In both, the co-occurrence partially reflected a shared liability but, in girls, genetic influences played an important role in the comorbidity involving depression, whereas in both sexes (but especially in boys) environmental factors played a substantial role. The extent to which these differences reflect genuine differences in the causal mechanisms underlying substance use and CD/depression in boys and girls revealed in the present analysis awaits replication from studies of other general population samples.

Adolescent↗

PubMed2003

Resolving multiple epigenetic pathways to adolescent depression.

BACKGROUND: Genotype x environment interaction (G x E) arises when genes influence sensitivity to the environment. G x E is easily recognized in experimental organisms that permit randomization of genotypes over fixed environmental treatments. Genotype-environment correlation (rGE) arises when genetic effects create or evoke exposure to environmental differences. Simultaneous analysis of G x E and such 'active' or 'evocative' rGE in humans is intractable with linear structural models widely used in behavioral genetics because environments are random effects often correlated with genotype. The causes of the environmental variation, therefore, need to be modeled at the same time as the primary outcome. METHODS: A Markov Chain Monte Carlo approach is used to resolve three distinct pathways involving genes and life events affecting the development of post-pubertal depression in female twins and its relationship to pre-pubertal anxiety: 1) the main of genes and environment; 2) the interaction of genes and environment (G x E); and 3) genotype-environment correlation (rGE). RESULTS: A model including G x E and rGE in addition to the main effects of genes and environment yields significant estimates of the parameters reflecting G x E and rGE. Omission of either G x E or rGE leads to overestimation of the effects of the measured environment and the unique random environment within families. CONCLUSIONS: 1) Genetic differences in anxiety create later genetic differences in depression; 2) genes that affect early anxiety increase sensitivity (G x E) to adverse life events; 3) genes that increase risk to early anxiety increase exposure to depressogenic environmental influences (rGE). Additional genetic effects, specific to depression, further increase sensitivity to adversity. Failure to take into account the effects of G x E and rGE will lead to misunderstanding how genes and environment affect complex behavior.

Adolescent↗

PubMed2003

Has the "Equal Environments" assumption been tested in twin studies?

A recurring criticism of the twin method for quantifying genetic and environmental components of human differences is the necessity of the so-called "equal environments assumption" (EEA) (i.e., that monozygotic and dizygotic twins experience equally correlated environments). It has been proposed to test the EEA by stratifying twin correlations by indices of the amount of shared environment. However, relevant environments may also be influenced by genetic differences. We present a model for the role of genetic factors in niche selection by twins that may account for variation in indices of the shared twin environment (e.g., contact between members of twin pairs). Simulations reveal that stratification of twin correlations by amount of contact can yield spurious evidence of large shared environmental effects in some strata and even give false indications of genotype x environment interaction. The stratification approach to testing the equal environments assumption may be misleading and the results of such tests may actually be consistent with a simpler theory of the role of genetic factors in niche selection.

Computer Simulation↗

PubMed2002

Depression scale scores in 8-17-year-olds: effects of age and gender.

BACKGROUND: The excess of unipolar depression in females emerges in adolescence. However, studies of age effects on depression scale scores have produced divergent estimates of changes from childhood to adolescence. METHOD: We explored possible reasons for this discrepancy in two large, longitudinal samples of twins and singletons aged 8-17. RESULTS: There were no differences between twins and singletons in their scores on the Short Mood and Feelings Questionnaire (SMFQ), a 13-item self-report depression scale. SMFQ scores for boys fell over this age-range, while those for girls fell from age 9 to age 11 and then increased from age 12 to age 17. The mean scores of girls under 12 and those 12 and over differed by only around one-fifth of a standard deviation. However, given the non-normal distribution of the scores, a cut point that selected the upper 6% of scores created the expected female:male ratio of 2:1. CONCLUSIONS: Implications for future research on adolescent depression are discussed.

Adolescent↗