Stable Genetic Effects on Symptoms of Alcohol Abuse and Dependence from Adolescence into Early Adulthood

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.     

The Genetic and Environmental Etiology of Antisocial Behavior from Childhood to Emerging Adulthood

Previous research suggests that both genetic and environmental influences are important for antisocial behavior across the life span, even though the prevalence and incidence of antisocial behavior varies considerably across ages. However, little is known of how genetic and environmental effects influence the development of antisocial behavior. A total of 2,600 male and female twins from the population-based Swedish Twin Registry were included in the present study. Antisocial behavior was measured on four occasions, when twins were 8–9, 13–14, 16–17, and 19–20 years old. Longitudinal analyses of the data were conducted using structural equation modeling. The stability of antisocial behavior over time was explained by a common latent persistent antisocial behavior factor. A common genetic influence accounted for 67% of the total variance in this latent factor, the shared environment explained 26%, and the remaining 7% was due to the non-shared environment. Significant age-specific shared environmental factors were found at ages 13–14 years, suggesting that common experiences (e.g., peers) are important for antisocial behavior at this age. Results from this study show that genetic as well as shared environmental influences are important in antisocial behavior that persists from childhood to emerging adulthood.     

Internalizing Behavior in Adolescent Girls Affects Parental Emotional Overinvolvement: A Cross-lagged Twin Study

The aim of this study was to examine the direction and the etiology of the association between different parenting styles (parental emotional overinvolvement [EOI] and parental criticism) and internalizing behavior from adolescence to early adulthood. A longitudinal genetically informative cross-lagged design was applied to a population-based sample of Swedish twins contacted at age 16–17 (n = 2369) and at age 19–20 (n = 1705). Sex-limitation modelling revealed different effects for boys and girls. For girls, genetic influences on internalizing problems at age 16–17 independently explained 2.7% of the heritability in parental EOI at age 19–20. These results suggest that emotionally overinvolved and self-sacrificing parental behavior stems in part from daughters (but not sons) genetic predisposition for internalizing behavior. These findings highlight the importance of genetically influenced child-driven effects underlying the parenting-internalizing association, and clarify that the role of such effects may differ depending on sex, type of parenting and developmental period.     

Genetic and Environmental Influences on the Stability of Withdrawn Behavior in Children: A Longitudinal,Multi-informant Twin Study

We examined the contribution of genetic and environmental influences on the stability of withdrawn behavior (WB) in childhood using a longitudinal multiple rater twin design. Maternal and paternal ratings on the withdrawn subscale of the Child Behavior Checklist (CBCL) were obtained from 14,889 families when the twins were 3, 7, 10 and 12 years old. A longitudinal psychometric model was fitted to the data and the fit of transmission and common factor models were evaluated for each variance component. WB showed considerable stability throughout childhood, with correlation coefficients ranging from about .30 for the 9-year time interval to .65 for shorter time intervals. Individual differences in WB as observed by the mother and the father were found to be largely influenced by genetic effects at all four time points, in both boys (50–66%) and girls (38–64%). Shared environmental influences explained a small to modest proportion (0–24%) of the variance at all ages and were slightly more pronounced in girls. Non-shared environmental influences were of moderate importance to the variance and slightly increased with age, from 22–28% at age 3 to 35–41% at age 12 years. The stability of WB was largely explained by genetic effects, accounting for 74% of stability in boys and 65% in girls. Shared environmental effects explained 7% (boys) and 17% (girls) of the behavioral stability. Most shared environmental effects were common to both raters, suggesting little influence of rater bias in the assessment of WB. The shared environmental effects common to both raters were best described by a common factor model, indicating that these effects are stable and persistent throughout childhood. Non-shared environmental effects accounted for the remaining covariance over time. Edited by Hermine Maes.     

Heritability and Longitudinal Stability of Schizotypal Traits During Adolescence

The study investigated the genetic and environmental etiology of schizotypal personality traits in a non-selected sample of adolescent twins, measured on two occasions between the ages of 11 and 16 years old. The 22-item Schizotypal Personality Questionnaire- Child version (SPQ-C) was found to be factorially similar to the adult version of this instrument, with three underlying factors (Cognitive-Perceptual, Interpersonal-Affective, and Disorganization). Each factor was heritable at age 11–13 years (h ² = 42–53%) and 14–16 years old (h ² = 38–57%). Additive genetic and unique environmental influences for these three dimensions of schizotypal personality acted in part through a single common latent factor, with additional genetic effects specific to both Interpersonal-Affective and Disorganization subscales at each occasion. The longitudinal correlation between the latent schizotypy factor was r = 0.58, and genetic influences explained most of the stability in this latent factor over time (81%). These longitudinal data demonstrate significant genetic variance in schizotypal traits, with moderate stability between early to middle adolescence. In addition to common influences between the two assessments, there were new genetic and non-shared environmental effects that played a role at the later assessment, indicating significant change in schizotypal traits and their etiologies throughout adolescence.     

Genetic and Environmental Causes of Variation in Trait Resilience in Young People

The aim of this multi-informant twin study was to determine the relative role of genetic and environmental factors in explaining variation in trait resilience in adolescents. Participants were consenting families (N = 2,638 twins in 1,394 families), from seven national cohorts (age 12–18 years, both sexes) of monozygotic and dizygotic twins reared together. Questionnaire data on the adolescents’ Ego-resilience (ER89) was collected from mothers, fathers and twins, and analysed by means of multivariate genetic modelling. Variance in trait resilience was best represented in an ADE common pathways model with sex limitation. Variance in the latent psychometric resilience factor was largely explained by additive genetic factors (77% in boys, 70% in girls), with the remaining variance (23 and 30%) attributable to non-shared environmental factors. Additive genetic sources explained more than 50% of the informant specific variation in mothers and fathers scores. In twins, additive and non-additive genetic factors together explained 40% and non-shared environmental factor the remaining 60% of variation. In the mothers’ scores, the additive genetic effect was larger for boys than for girls. The non-additive genetic factor found in the twins’ self ratings was larger in boys than in girls. The remaining sex differences in the specific factors were small. Trait resilience is largely genetically determined. Estimates based on several informants rather than single informants approaches are recommended.     

Heritability of Self-reported Phobic Fear

Twin studies on fear and phobia suggest moderate genetic effects. However, results are inconclusive regarding the presence of dominant genetic effects and sex differences. Using an extended twin design, including male and female twins (n = 5,465) and their siblings (n = 1,624), we examined the genetic and environmental influences on blood-injury, social, and agoraphobic fear and investigated their interaction with sex and age. Data of spouses (n = 708) of twins were used to evaluate assortative mating for the three fear dimensions. Results showed that there was no assortative mating for blood-injury, social and agoraphobic fear. Resemblance between biological relatives could be explained by additive and non-additive genetic effects for blood-injury and agoraphobic fear in all participants, and social fear in participants aged 14–25 years. For social fear in participants aged 26–65 only additive genetic effects were detected. Broad-sense heritability estimates ranged from 36 to 51% and were similar for men and women. Edited by John K Hewitt.     

Genetic and Environmental Factors Influencing BMI Development from Adolescence to Young Adulthood

BMI increases progressively from adolescence to young adulthood. The aims of the present study were firstly, to investigate the extent to which genetic and environmental influences account for differences in BMI trajectories during this period, and secondly to examine whether boys and girls show divergences in these influences, as their BMI normally start differing across adolescence. The study sample consisted of 4,915 monozygotic and like- and unlike-sex dizygotic twins, born between 1975 and 1979. Data on BMI was gathered when twins were on average 16.1, 17.1, 18.6 and 24.4 years old. Genetic and environmental influences on the BMI trajectories were modeled using a latent growth curve approach. The results showed that the heritability of BMI decreased slightly after the adolescence period, from ≈80 to 70%. BMI transition from adolescence to young adulthood was best described by a quadratic trajectory that was highly accounted (61.7–86.5%) for by additive genetic influences. Genetic influences on BMI level showed a low correlation with those on the trend in BMI with age indicating that different sets of genes underlie the change of BMI during this period. Importantly, the analyses also evidenced that different genetic and environmental influences may underlie boys and girls evolution. In conclusion, our results suggested specific genetic influences accounting for the BMI rate-of-change from adolescence to young adulthood. This indicates that the specific genes behind BMI level may not be the same as the genes affecting BMI change which should be taken into account in further efforts to identify these genes.     

The Familial Clustering of Age at Menarche in Extended Twin Families

The timing of puberty is complex, possibly involving many genetic factors that may interact with environmental influences. Familial resemblance for age at menarche was studied in a sample of 4,995 female twins, 1,296 sisters, 2,946 mothers and 635 female spouses of male twins. They had indicated their age at menarche as part of a larger longitudinal survey. We assessed assortative mating for age at menarche, gene–environment interaction effects and estimated the heritability of individual differences in pubertal timing. There was significant evidence of gene–environment interaction, accounting for 1.5% of the variance. There was no indication of consistent mate assortment on age at menarche. Individual differences in age at menarche are highly heritable, with additive genetic factors explaining at least 70% of the true variation. An additional 1.5% of the variation can be explained by a genotype–environment interaction effect where environmental factors are more important in individuals genetically predisposed for late menarche. Edited by Stacey Cherny     

Age Differences in Genetic and Environmental Variations in Stress-Coping During Adulthood: A Study of Female Twins

The way people cope with stressors of day to day living has an important influence on health. The aim of the present study was to explore whether genetic and environmental variations in stress-coping differ over time during adulthood. The brief COPE was mailed to a large sample of the UK female twins (N = 4,736) having a wide range of age (20–87 years). Factor analyses of the items of the brief COPE yielded three coping scales: ‘Problem-Solving’, ‘Support Seeking’, and ‘Avoidance’. Monozygotic and dizygotic twin correlations tended to become lower with age for all three scales, suggesting that unique environmental factors may become more important with age during adulthood. Model-fitting results showed that relative influences of unique environmental factors increased from 60 % at age 20 years to 74% at age 87 years for ‘Problem-Solving’ and 56 % at age 20 years to 76% at age 87 years for ‘Avoidance’. During the same age period, genetic factors decreased from 40 to 26 % for ‘Problem-Solving’ and from 44 to 24 % for ‘Avoidance’. For ‘Seeking Support’, the magnitude of genetic and unique environmental factors was not significantly different across the adulthood. For all three scales, shared environmental effects were negligible. Overall, our findings implicate that the effects of environment that stem from idiosyncratic experience of stressful life events accumulate and become increasingly important in adulthood.     

Genes and Developmental Stabiltiy of Aggressive Behavior Problems at Home and School in a Community Sample of Twins Aged 7–12

Though behavioral genetic studies of aggression have implicated heritable and environmental factors, there is limited understanding of how these factors influence aggression across different settings and over time. Ratings for 732 twins were collected from parents and teachers during middle childhood and early adolescence. Total aggression scores on the Child Behavioral Checklist (CBCL) and Teacher Report Form (TRF) were examined at each age, across both settings, and developmentally. In this sample, aggressive behavior was moderately to largely heritable at each age within the home (.76–.84) and school (.42–.61). Across each age, ratings by parents and teachers were moderately correlated (.19–.36). Genetic and environmental effects that were limited to a particular setting were important etiological factors for aggressive behavior consistently within each setting, while only genetic factors influenced levels of aggression across both settings. Stability during these ages was due to genetic effects common to each age and the persistence of child-specific environmental experiences within each setting. These results suggest that genetic and environmental influences on children’s aggressive behavior are largely setting specific. Levels of aggression seen consistently across both settings are due to genetic influences. Developmentally stable levels of aggressive behavior result from genetic influences common to all ages and individual environmental influences whose effects persist across ages.Edited by Danielle Posthuma     

Depressive Symptoms and Alcohol Use are Genetically and Environmentally Correlated Across Adolescence

Depressive symptoms and alcohol use are frequently positively associated during adolescence. This study aimed to assess the heritability of each phenotype across adolescence; to assess potential shared liabilities; to examine changes in the nature of shared liabilities across adolescence; and to investigate potential causal relationships between depressive symptoms and alcohol use. We studied a longitudinally assessed sample of adolescent Finnish twins (N = 1,282) to test hypotheses about genetic and environmental influences on these phenotypes within and across ages, using data from assessments at ages 12, 14, and 17.5 years. The heritability of depressive symptoms is consistent across adolescence (~40–50%), with contributions from common and unique environmental factors. The heritability of alcohol use varies across time (a² = .25–.44), and age 14 alcohol use is heavily influenced by shared environmental factors. Genetic attenuation and innovation were observed across waves. Modest to moderate genetic (r_A = .26–.59) and environmental (r_C = .30–.63) correlations between phenotypes exist at all ages, but decrease over time. Tests for causal relationships between traits differed across ages and sexes. Intrapair MZ difference tests provided evidence for reciprocal causation in girls at ages 14 and 17.5. Formal causal models suggested significant causal relationships between the variables in both boys and girls. The association between depressive symptoms and alcohol use during adolescence is likely due to a combination of shared genetic and environmental influences and causal influences. These influences are also temporally dynamic, complicating efforts to understand factors contributing to the relationship between these outcomes.     

Endophenotypes in a Dynamically Connected Brain

We examined the longitudinal genetic architecture of three parameters of functional brain connectivity. One parameter described overall connectivity (synchronization likelihood, SL). The two others were derived from graph theory and described local (clustering coefficient, CC) and global (average path length, L) aspects of connectivity. We measured resting state EEG in 1,438 subjects from four age groups of about 16, 18, 25 and 50 years. Developmental curves for SL and L indicate that connectivity is more random at adolescence and old age, and more structured in middle-aged adulthood. Individual variation in SL and L were moderately to highly heritable at each age (SL: 40–82%; L: 29–63%). Genetic factors underlying these phenotypes overlapped. CC was also heritable (25–49%) but showed no systematic overlap with SL and L. SL, CC, and L in the alpha band showed high phenotypic and genetic stability from 16 to 25 years. Heritability for parameters in the beta band was lower, and less stable across ages, but genetic stability was high. We conclude that the connectivity parameters SL, CC, and L in the alpha band show the hallmarks of a good endophenotype for behavior and developmental disorders.     

A Multivariate Twin Study of Autistic Traits in 12-Year-Olds: Testing the Fractionable Autism Triad Hypothesis

Autistic traits—social impairment, communication impairment, and restricted and repetitive behaviors and interests—are heritable in the general population. Previous analyses have consistently reported limited genetic and environmental overlap between autistic trait domains in samples assessed in middle childhood. Here we extend this research to parent-report data for 12-year-olds. Data from 5,944 pairs in the Twins Early Development Study were analyzed to explore the domain-specific heritability and degree of shared genetic and environmental influences across different autistic traits in the general population and among individuals scoring in the top 5% of each domain. Sex differences in the etiological estimates were also tested in these analyses. Autistic traits were moderately to highly heritable (0.58–0.88) at age 12. Bivariate genetic correlations in the full sample (0.18–0.40) and the extremes (0.24–0.67), as well as even lower unique environmental correlations, all suggested considerable fractionation of genetic and environmental influences across autistic trait domains, in line with previous findings.     

Stability and Change of Genetic and Environmental Effects on the Common Liability to Alcohol, Tobacco, and Cannabis DSM-IV Dependence Symptoms

This study investigated the stability of genetic and environmental effects on the common liability to alcohol, tobacco, and cannabis dependence across adolescence and young adulthood. DSM-IV symptom counts from 2,361 adolescents were obtained using a structured diagnostic interview. Several sex-limited longitudinal common pathway models were used to examine gender differences in the magnitude of additive genetic (A), shared environment, and non-shared environmental effects over time. Model fitting indicated limited gender differences. Among older adolescents (i.e., age >14), the heritability of the latent trait was estimated at 0.43 (0.05, 0.94) during the first wave and 0.63 (0.21, 0.83) during the second wave of assessment. A common genetic factor could account for genetic influences at both assessments, as well as the majority of the stability of SAV over time [rA = 1.00 (0.55, 1.00)]. These results suggest that early genetic factors continue to play a key role at later developmental stages.     

Identification of chromosomal regions linked to premature myocardial infarction: a meta-analysis of whole-genome searches

Myocardial infarction (MI) is a complication of coronary artery disease and the leading cause of death in the Western world. MI is considered a distinct phenotype with an increased genetic component for its premature type. MI’s exact inheritance pattern is still unknown. Genome searches for identifying susceptibility loci for premature MI produced inconclusive or inconsistent results. Thus, a genome search meta-analysis (GSMA) was applied to available genome search data on premature MI. GSMA is a non-parametric method to identify genetic regions that rank high, on average in terms of linkage statistics across genome searches unweighted or weighted by study size. The significance of each region’s average and heterogeneity, unadjusted or adjusted by neighbouring average simulated ranks, was calculated using a Monte Carlo test. The meta-analysis involved five genome searches in Caucasians. Eight regions (6p22.3–6p21.1, 14p13–14q13.1, 13q33.1–13q34, 5p15.33–5p15.1, 8q13.2–8q22.2, 1p36.21–1p35.2, 12q24.31–12q24.33, 8q24.21–8q24.3) were found to have significant average rank by either unweighted or weighted analyses. In addition, region 8q24.21–8q24.3 produced significant low heterogeneity (P _unadjusted=0.03 and P _adjusted=0.05). Four regions (6p22.3–6p21.1, 14p13–14q13.1, 8q13.2–8q22.2, 8q24.21–8q24.3) were not identified by the individual studies. The meta-analysis suggests that these four regions should be further investigated for genes that confer susceptibility to MI.     

Stable Genes and Changing Environments: Body Mass Index Across Adolescence and Young Adulthood

The transition between adolescence and young adulthood is a developmentally sensitive time where children are at an increased risk for becoming overweight and developing obesity. Twin studies have reported that body mass index [BMI] is highly heritable, however, it remains unclear whether the genetic influences are sex-limited and whether non-additive genetic influences contribute to body mass index [BMI] during these ages. In the current report, we examined self-reported data on BMI in same [n = 2,744] and opposite-sex [n = 1,178] siblings participating in the National Longitudinal Study on Adolescent Health [Add Health]. To investigate whether the same or different genes contributed to BMI for both sexes, we fit quantitative sex-limited genetic models to three waves of data collection. At each of the three Waves of assessment, models that included additive genetic, individual-specific environment, and no sex-limited genetic influences fit the data most parsimoniously. Heritable effects on BMI at each of the three Waves were large for both sexes and ranged between .75 and .86. While genetic contributions across the ages were highly correlated, longitudinal analyses indicated that the relevant individual-specific environmental influences on BMI in adolescence and young adulthood change sizably. These results underscore the importance of understanding early genetic influences on BMI and highlight the role environmental experiences have at later ages when new genetic influences appear to make a small contribution to individual variation in BMI.     

Heritability of somatotype components from early adolescence into young adulthood: a multivariate analysis on a longitudinal twin study

BACKGROUND: Several studies with different designs have attempted to estimate the heritability of somatotype components. However they often ignore the covariation between the three components as well as possible sex and age effects. Shared environmental factors are not always controlled for. AIM: This study explores the pattern of genetic and environmental determination of the variation in Heath-Carter somatotype components from early adolescence into young adulthood. SUBJECTS AND METHODS: Data from the Leuven Longitudinal Twin Study, a longitudinal sample of Belgian same-aged twins followed from 10 to 18 years (n = 105 pairs, equally divided over five zygosity groups), is entered into a multivariate path analysis. Thus the covariation between the somatotype components is taken into account, gender heterogeneity can be tested, common environmental influences can be distinguished from genetic effects and age effects are controlled for. RESULTS: Heritability estimates from 10 to 18 years range from 0.21 to 0.88, 0.46 to 0.76 and 0.16 to 0.73 for endomorphy, mesomorphy and ectomorphy in boys. In girls, heritability estimates range from 0.76 to 0.89, 0.36 to 0.57 and 0.57 to 0.76 for the respective somatotype components. Sex differences are significant from 14 years onwards. More than half of the variance in all somatotype components for both sexes at all time points is explained by factors the three components have in common. CONCLUSIONS: The finding of substantial genetic influence on the variability of somatotype components is further supported. The need to consider somatotype as a whole is stressed as well as the need for sex- and perhaps age-specific analyses. Further multivariate analyses are needed to confirm the present findings.     

Changes in genetic and environmental influences on trait anxiety from middle adolescence to early adulthood

Background

Middle adolescence to early adulthood is an important developmental period for the emergence of anxiety. Genetically-influenced stable traits are thought to underlie internalizing psychopathology throughout development, but no studies have examined changes in genetic and environmental influences on trait anxiety during this period.

Method

A longitudinal twin study design was used to study same-sex twin pairs (485 monozygotic pairs, 271 dizygotic pairs) at three ages, 14, 18, and 21 years, to examine developmental shifts in genetic and environmental effects on trait anxiety.

Results

The heritability of trait anxiety increased with age, particularly between ages 14 and 18, no significant new genetic influences emerged after age 14, and the genetic influences were highly correlated across the three ages, supporting developmentally stable genetic risk factors. The environmental effects shared by members of a family decreased in influence across adolescence, while the influence of environmental effects unique to each individual twin remained relatively stable over the course of development and were largely age-specific.

Limitations

The twin study design does not inform about specific genes and environmental risk factors.

Conclusions

Genetic influences increased in importance from middle to late adolescence but common genetic factors influenced trait anxiety across the three ages. Shared environmental influences decreased in importance and demonstrated negligible influence by late adolescence/early adulthood. Nonshared environmental effects were almost entirely age-specific. These findings support the importance of developmentally-sensitive interventions that target shared environmental factors prior to middle adolescence and shifting non-shared environmental risks at each age.