Differences In Genetic Influences Research Articles

Estrogen moderation of genetic influences on eating disorder symptoms during gonadarche in girls: Specific effects on binge eating

The heritability of eating disorder (ED) symptoms increases dramatically across gonadarche in girls. Past studies suggest these developmental differences could be due to pubertal activation of estrogen, but findings have been limited to only one ED symptom (i.e., binge eating). The current study examined whether estrogen contributes to gonadarcheal differences in genetic influences on overall levels of ED symptoms as well as key cognitive symptoms (i.e., weight/shape concerns) that are present across all EDs and are early risk factors for eating pathology. Given that binge eating frequently co-occurs with all of these symptoms, analyses also examined whether estrogen effects exist for overall levels of ED symptoms and body weight/shape concerns after accounting for the known effects of estrogen on genetic risk for binge eating. Participants included 964 female twins (ages 8-16) from the Michigan State University Twin Registry. Overall levels of ED symptoms were assessed with the Minnesota Eating Behavior Survey (MEBS) total score. Weight/shape concerns were assessed with a latent factor modeled using subscales from the MEBS and the Eating Disorder Examination Questionnaire. Estradiol levels were assessed with saliva samples. Twin moderation models were used to examine whether genetic influences on overall levels of ED symptoms and weight/shape concerns differed significantly across estradiol levels. Although initial models suggested modest differences in genetic influences on overall levels of ED symptoms across estradiol levels, these effects were eliminated when binge eating was accounted for in the models. In addition, weight/shape concerns did not show significant moderation of genetic influences by estradiol in models with or without binge eating. Taken together, results are significant in suggesting that individual differences in estradiol levels during gonadarche have a unique and specific impact on genetic risk for binge eating, while other etiologic factors must contribute to increased heritability of cognitive ED symptoms during this key developmental period in girls.

Estrogen moderates genetic influences on binge eating during puberty: Disruption of normative processes?

Puberty is a critical period for changes in genetic effects for binge eating in girls. Previous twin studies show increases in genetic influences on binge eating from prepuberty (∼0%) to midpuberty and beyond (∼50%). However, little is known about the factors that drive these shifts in genetic effects. A small pilot study showed that pubertal activation of estrogen may contribute to increases in genetic influences, possibly via hormonally induced changes in gene expression. However, large-scale studies investigating hormone effects on genetic risk are lacking. Thus, the purpose of the present study was to examine the effects of estrogen on genetic influences for binge eating in 964 female twins (ages 8-16 years) from the Michigan State University Twin Registry. Binge eating was assessed with the Minnesota Eating Behaviors Survey, whereas afternoon saliva samples were assayed for estradiol levels using standard enzyme immunoassays. Twin moderation models showed substantial differences in genetic influences on binge eating across estradiol levels. Stronger genetic effects were observed at lower (rather than higher) estradiol levels, even when controlling for the effects of age, body mass index, the physical changes of puberty, and the onset of menses. Overall, findings suggest that comparatively lower levels of estradiol during this critical period may disrupt normative developmental processes and enhance genetic influences on binge eating. (PsycINFO Database Record

Neural outcome processing of peer-influenced risk-taking behavior in late adolescence: Preliminary evidence for gene × environment interactions.

Adolescent brains are particularly susceptible to the rewarding properties of risky decisions in social contexts. Individual differences in genetic influences on dopamine transmission moderate neural outcome processing of risky decisions and may exert pronounced effects on adolescent risk-taking behavior (RTB) and corresponding neural outcome processing in peer contexts, a process called gene-environment interaction (G × E). Eighty-five undergraduate students completed a behavioral risk task alone and in the presence of a confederate peer providing "risky" feedback. We tested for G × E effects using a polygenic risk index that included 3 candidate genetic variations associated with high dopamine transmission efficiency, as well as the moderating role of family history of behavioral disinhibition. Difference waves for the P300 and FRN (i.e., feedback-related negativity) were examined as indices of neural outcome processing. A G × E effect was observed for RTB and the P300, but not the FRN. Family history of behavioral disinhibition also interacted with peer influence to predict P300 amplitude. These data provide preliminary evidence for G × E for peer-influenced RTB and neural outcome processing during late adolescence. Genetic influences on dopaminergic function may be particularly relevant for attentional and motivational neural systems, as indexed by the P300, which exert downstream effects on peer-influenced RTB. (PsycINFO Database Record

Genetic topography of brain morphology

Animal data show that cortical development is initially patterned by genetic gradients largely along three orthogonal axes. We previously reported differences in genetic influences on cortical surface area along an anterior-posterior axis using neuroimaging data of adult human twins. Here, we demonstrate differences in genetic influences on cortical thickness along a dorsal-ventral axis in the same cohort. The phenomenon of orthogonal gradations in cortical organization evident in different structural and functional properties may originate from genetic gradients. Another emerging theme of cortical patterning is that patterns of genetic influences recapitulate the spatial topography of the cortex within hemispheres. The genetic patterning of both cortical thickness and surface area corresponds to cortical functional specializations. Intriguingly, in contrast to broad similarities in genetic patterning, two sets of analyses distinguish cortical thickness and surface area genetically. First, genetic contributions to cortical thickness and surface area are largely distinct; there is very little genetic correlation (i.e., shared genetic influences) between them. Second, organizing principles among genetically defined regions differ between thickness and surface area. Examining the structure of the genetic similarity matrix among clusters revealed that, whereas surface area clusters showed great genetic proximity with clusters from the same lobe, thickness clusters appear to have close genetic relatedness with clusters that have similar maturational timing. The discrepancies are in line with evidence that the two traits follow different mechanisms in neurodevelopment. Our findings highlight the complexity of genetic influences on cortical morphology and provide a glimpse into emerging principles of genetic organization of the cortex.

Genetic and Environmental Influences on Longitudinal Changes in Leisure-Time Physical Activity From Adolescence to Young Adulthood

The aim of this study was to estimate genetic and environmental influences on the longitudinal evolution of leisure-time physical activity habits from adolescence to young adulthood. Data were gathered at four time points, at mean ages 16.2, 17.1, 18.6, and 24.5 years. At baseline, the sample comprised 5,216 monozygotic and dizygotic twins, born 1975-1979, and, at the last follow-up point, of 4,531 monozygotic and dizygotic twins. Physical activity volume was assessed as frequency of leisure-time physical activity and participants were categorized into three groups: inactive, moderately active, and active. Genetic and environmental influences were estimated using a multivariate, longitudinal Cholesky decomposition with a 'multifactorial liability threshold' approach. The results suggest that, in both sexes the heritability of leisure-time physical activity remained moderate (~43-52%) during adolescence, declining to ~30% in young adulthood. Shared environmental influences increased from adolescence (~18-26%) to young adulthood (43% in men and 49% in women). Specific environmental influences remained relatively stable during the total follow-up (~20-30%). New genetic, shared, and specific environmental influences at every follow-up point were suggested by the low correlations across occasions. In conclusion, the study demonstrated gender differences in genetic influences in the evolution of leisure-time physical activity habits from adolescence to young adulthood. However, shared environmental influences, especially in women, were crucial in explaining longitudinal changes in leisure-time physical activity. These outcomes emphasize the need of gender-specific measures to promote physical activity habits during young adulthood.

The effects of puberty on genetic risk for disordered eating: evidence for a sex difference.

Differences in genetic influences on disordered eating are present across puberty in girls. Heritability is 0% before puberty, but over 50% during and after puberty. Emerging data suggest that these developmental differences may be due to pubertal increases in ovarian hormones. However, a critical piece of evidence is lacking, namely, knowledge of genetic influences on disordered eating across puberty in boys. Boys do not experience increases in ovarian hormones during puberty. Thus, if pubertal increases in genetic effects are present in boys, then factors in addition to ovarian hormones may drive increases in heritability in girls. The current study was the first to examine this possibility in a sample of 1006 male and female twins from the Michigan State University Twin Registry. Disordered eating was assessed with the Minnesota Eating Behavior Survey. Pubertal development was assessed with the Pubertal Development Scale. No significant differences in genetic influences on disordered eating were observed in males across any developmental stage. Heritability was 51% in boys during pre-puberty, puberty and young adulthood. By contrast, in girls, genetic factors accounted for 0% of the variance in pre-puberty, but 51% of the variance during puberty and beyond. Sex differences in genetic effects were only significant during pre-puberty, as the best-fitting models constrained heritability to be equal across all males, pubertal females and young adult females. The results highlight sex-specific effects of puberty on genetic risk for disordered eating and provide indirect evidence of a role for ovarian hormones and/or other female-specific factors.

Developmental structure of genetic influences on antisocial behavior across childhood and adolescence.

It is necessary to determine if causal influences on developing antisocial behavior change with age to guide both research and theory on its origins. The extent to which the same genetic factors influence antisocial behavior across 4-17 years of age was estimated using 2,482 sibling pairs of varying genetic relatedness. Assessments of antisocial behavior by mothers (4-9 years), mothers and youth (10-13 years), and youth (14-17 years) reflected the changing validity of informants across development. Genetic influences on antisocial behavior at 14-17 years were entirely shared with those on antisocial behavior at 10-13 years according to both informants. Genetic influences on antisocial behavior at 14-17 years were distinct from those at 4-9 years, however. These age differences in genetic influences cannot be fully distinguished from informant differences across age, but the present findings indicate that youth reported to be persistently antisocial during childhood and adolescence are influenced by one set of genetic factors influencing parent-report conduct problems in childhood and a second set of genetic influences on youth-reported delinquency that come into play around the time of the pubertal transition.

Sex distinctiveness in effective genotype.

The difference between sexes in incidence and prevalence of alcohol-related problems is a central feature of alcohol research. It is inevitable that these differences will receive escalating attention as it becomes increasingly apparent that the interests of both equity and good science are served by the study of sex differences in health-related processes. For several reasons, genetic methods promise to offer powerful tools for the elucidation of sex differences. In the first place, the determination of sex depends on a genetic mechanism. Furthermore, there is an abundant literature showing the relevance of heredity to a broad variety of alcohol-related processes. Moreover, there is evidence of major differences in genetic influences in males and females in respect to alcoholism specifically. It is important to appreciate that genetic influence on sex distinctiveness may operate through several different mechanisms, with quite different implications. The purpose of this chapter is to provide an elementary description of these different genetic routes to sex differences.

Genetic variation in bone mineral density and calcaneal ultrasound: a study of the influence of menopause using female twins.

The aim of the study was to determine whether the genetic variance in bone mineral density (BMD) and calcaneal ultrasound differs in pre- and postmenopausal women and to establish whether the genes operating before the menopause are the same as those after the menopause. Twins aged 18-75 years were recruited from the St Thomas' UK Adult Twin Registry. Quantitative model fitting techniques were used to test for differences in genetic influences in pre- and postmenopausal twins of several BMD sites and calcaneal ultrasound measures accounting for age. BMD and heel ultrasound variables were measured in 2490 female twins: 360 monozygotic pairs and 885 dizygotic pairs. The heritability in the group overall ranged from 19% to 76%. A significant increase in total variance was seen for most BMD sites after the menopause. The proportion of total variance explained by genetic influence was higher premenopausally at all sites except the femoral neck. For example, the genetic proportion of total variance for spine BMD was 88% premenopausally and 77% postmenopausally. In contrast there was no significant difference in total variance of ultrasound measures with menopause. There was no indication that traits are influenced by different genes before and after menopause. This study demonstrates that genetic and environmental influences differ significantly in pre- and postmenopausal groups for BMD, but not for calcaneal ultrasound. The total variance in BMD is greater postmenopausally, but there is evidence that the same genes are involved. These data stress the importance of accounting for menopause-gene interactions in the genetic analysis of data on osteoporosis.

Influence of ascertainment strategy on finding sex differences in genetic estimates from twin studies of alcoholism

Twin studies have yielded contradictory findings about sex differences in genetic influences on the etiology of alcoholism. Studies based on population registers or epidemiological samples have yielded similar estimates of heritability (50–60% of the total variance) for males and females. In contrast, studies of twins identified through treatment settings have found sizeable genetic contributions to alcoholism in males but usually negligible heritabilities for females. We investigated this discrepancy by applying a “simulated” treatment ascertainment strategy to data on alcohol-related disorders collected by structured interviews with a population-based sample of adult twins aged 18–56 years from the Mid-Atlantic Twin Registry. Structural models were used to estimate heritabilities for two definitions of treatment, and these estimates were compared with those obtained from the population-based sample. In males, heritability estimates were similar across sampling methods, but the treatment ascertainment methods yielded higher estimates of common environmental influences. For females, heritability estimates based on a broad definition of treatment were similar to those obtained by using the random ascertainment design. However, estimates based on sampling women who had been in alcohol-treatment programs were (nonsignificantly) lower than those obtained with the other methods. These results provide partial support for the hypothesis that differences in sampling method may account for differences in heritability estimates for alcoholism among studies of female twins. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:754–761, 2000. © 2000 Wiley-Liss, Inc.

Influence of ascertainment strategy on finding sex differences in genetic estimates from twin studies of alcoholism

Twin studies have yielded contradictory findings about sex differences in genetic influences on the etiology of alcoholism. Studies based on population registers or epidemiological samples have yielded similar estimates of heritability (50-60% of the total variance) for males and females. In contrast, studies of twins identified through treatment settings have found sizeable genetic contributions to alcoholism in males but usually negligible heritabilities for females. We investigated this discrepancy by applying a "simulated" treatment ascertainment strategy to data on alcohol-related disorders collected by structured interviews with a population-based sample of adult twins aged 18-56 years from the Mid-Atlantic Twin Registry. Structural models were used to estimate heritabilities for two definitions of treatment, and these estimates were compared with those obtained from the population-based sample. In males, heritability estimates were similar across sampling methods, but the treatment ascertainment methods yielded higher estimates of common environmental influences. For females, heritability estimates based on a broad definition of treatment were similar to those obtained by using the random ascertainment design. However, estimates based on sampling women who had been in alcohol-treatment programs were (nonsignificantly) lower than those obtained with the other methods. These results provide partial support for the hypothesis that differences in sampling method may account for differences in heritability estimates for alcoholism among studies of female twins. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:754-761, 2000.

Heritability of social cognitive skills in children and adolescents.

Social cognitive skills are those which enable understanding of social situations; they are relevant to a variety of psychiatric disorders including autism, schizophrenia and externalizing behaviour problems in children. To examine the heritability of social cognitive skills. Using a population-based sample of twins aged 5-17, the genetic and environmental influences on social cognitive skills were examined. Male scores were higher than female scores (P < 0.001), indicating poorer social cognition among males. A heritability of 0.68 (95% CI 0.43-0.78) was found, with shared environmental influences accounting for only 0.05 of the variance (95% CI 0.00-0.28). This could be removed from the model without worsening the fit. There were no significant differences in genetic effects between the genders, but age-related changes were found, with younger twins showing greater genetic influence on social cognition. Social cognition appears to be under considerable genetic influence in the population and shows significant male-female differences. No gender differences in genetic influences on the variance of scores were found, but the effects of age were significant.

Genes and Environment Have Gender-Independent Influences on the Eating and Drinking of Free-Living Humans

Males and females differ in the amounts of food and fluids they ingest. Previous studies suggest that this may be due to differences in genetic influences on intake. Gender differences in the heritability of food and fluid intake were investigated with 110 identical and 102 fraternal same-sex and 53 fraternal mixed-gender adult twin pairs who were paid to maintain 7-day food intake diaries. Linear structural modeling revealed significant genetic influences on the overall and meal intakes of foods and fluids and specific beverage and food types. No gender differences were found in the genes that influence intake or, for the most part, in the magnitude of the genetic influences on intake. However, gender differences were found for the between-meal intakes of fluids, being influenced by heredity for males but by common, familial, environment for females. The data suggest that intakes are equivalently influenced by inheritance and individual environment for both males and females and that most gender differences are due to a simple multiplicative difference between intakes possibly due to body size and/or caloric expenditure differences.

Genetic and environmental contributions to alcohol dependence risk in a national twin sample: consistency of findings in women and men.

Genetic influences on alcoholism risk are well-documented in men, but uncertain in women. We tested for gender differences in genetic influences on, and risk-factors for, DSM-III-R alcohol dependence (AD). Diagnostic follow-up interviews were conducted in 1992-3 by telephone with twins from an Australian twin panel first surveyed in 1980-82 (N = 5889 respondents). Data were analysed using logistic regression models. Significantly higher twin pair concordances were observed in MZ compared to DZ same-sex twin pairs in women and men, even when data were weighted to adjust for over-representation of well-educated respondents, and for selective attrition. AD risk was increased in younger birth cohorts, in Catholic males or women reporting no religious affiliation, in those reporting a history of conduct disorder or major depression and in those with high Neuroticism, Social Non-conformity, Toughmindedness, Novelty-Seeking or (in women only) Extraversion scores; and decreased in 'Other Protestants', weekly church attenders, and university-educated males. Controlling for these variables, however, did not remove the significant association with having an alcoholic MZ co-twin, implying that much of the genetic influence on AD risk remained unexplained. No significant gender difference in the genetic variance in AD was found (64% heritability, 95% confidence interval 32-73%). Genetic risk-factors play as important a role in determining AD risk in women as in men. With the exception of certain sociocultural variables such as religious affiliation, the same personality, sociodemographic and axis I correlates of alcoholism risk are observed in women and men.

Genetic architecture of EEG power spectra in early life

We measured the electroencephalogram (EEG) in 209 5 year old monozygotic (MZ) and dizygotic (DZ) twin pairs to estimate the relative contribution of genetic and environmental factors to EEG power spectra in early life. Data from same-sex and from opposite-sex twin pairs were used to test for sex differences in genetic influences. Results showed high concordance for EEGs of MZ twins for absolute and relative power in delta, theta, alpha 1, alpha 2, beta 1 and beta 2 bands. A model with additive genetic and unique environmental influences explained individual differences in both absolute and relative power in almost all bands and all electrode positions. Heritability of EEG power spectra was high. For absolute power the highest heritabilities were observed in theta, alpha 1, alpha 2 and beta 1 power bands (mean heritability 81, 81, 78, and 73%, respectively). Somewhat lower heritabilities were found in delta and beta 2 bands (mean heritability 55 and 64%, respectively). For relative power heritabilities were 63, 76, 71, 72, 68, and 65 for delta, theta, alpha 1, alpha 2, beta 1, and beta 2, respectively. Virtually no sex differences in heritability were found. These findings indicate that the background EEG is one of the most heritable characteristics in early life.