Familial Clustering of Abdominal Visceral Fat and Total Fat Mass: The Québec Family Study

The evidence for common familial factors underlying total fat mass (estimated from underwater weighing) and abdominal visceral fat (assessed from CT scan) was examined in families participating in phase 2 of the Québec Family Study (QFS) using a bivariate familial correlation model. Previous QFS investigations suggest that both genetic (major and polygenic) and familial environmental factors influence each phenotype, accounting for between 55% to 71% of the phenotypic variance in fat mass, and between 55% to 72% for abdominal visceral fat The current study suggests that the bivariate familial effect ranges from 29% to 50%. This pattern suggests that there may be common familial determinants for abdominal visceral fat and total fat mass, as well as additional familial factors which are specific to each. The relatively high spouse cross-trait correlations usually suggest that a large percent of the bivariate familial effect may be environmental in origin. However, if mating is not random, then the spouse resemblance may reflect either genetic or environmental causes, depending on the source [i.e., through similar genes or cohabitation (environmental) effects]. Finally, there are significant sex differences in the magnitude of the familial cross-trait correlations involving parents, but not offspring, suggesting complex generation (i.e., age) and sex effects. For example, genes may turn on or off as a function of age and sex, and/or there may be an accumulation over time of effects due to the environment which may vary by sex. Whether the common familial factors are genetic (major and/or polygenic), environmental, or some combination of both, and whether the familial expression depends on sex and/or age warrants further investigation using more complex models.     

The influence of subjective sleep quality on the association between eveningness and depressive symptoms

Increasing evidence suggests that eveningness is associated with increased risk for depression. Eveningness, however, is also associated with poor sleep quality and the unique role of eveningness in depressive symptomatology remains to be elucidated. The goal of the current study, therefore, was to examine the inter-relationships between eveningness, subjective sleep quality and depressive symptoms in healthy participants free of current or previous depression and sleep disorder. Here, 167 healthy participants (mean age 24.16, 129/38 females/males) completed the reduced Morningness–Eveningness Questionnaire (rMEQ), the Pittsburgh Sleep Quality Index (PSQI) and the Centre for Epidemiological Studies Depression Scale (CES-D). Bootstrap mediation analysis for a simple mediation model including rMEQ, PSQI and CES-D was applied. Eveningness was associated with increased depressive symptoms and mediation analysis showed that this relationship was partly mediated by sleep quality. Our results suggest that indicators of depression observed in evening-type individuals cannot be attributed exclusively to disturbed sleep. We suggest that interventions that target both sleep quality and dysfunctional cognitive styles would be optimal to promote well-being in evening-type individuals.     

Etiology in psychiatry: embracing the reality of poly‐gene‐environmental causation of mental illness

Intriguing findings on genetic and environmental causation suggest a need to reframe the etiology of mental disorders. Molecular genetics shows that thousands of common and rare genetic variants contribute to mental illness. Epidemiological studies have identified dozens of environmental exposures that are associated with psychopathology. The effect of environment is likely conditional on genetic factors, resulting in gene‐environment interactions. The impact of environmental factors also depends on previous exposures, resulting in environment‐environment interactions. Most known genetic and environmental factors are shared across multiple mental disorders. Schizophrenia, bipolar disorder and major depressive disorder, in particular, are closely causally linked. Synthesis of findings from twin studies, molecular genetics and epidemiological research suggests that joint consideration of multiple genetic and environmental factors has much greater explanatory power than separate studies of genetic or environmental causation. Multi‐factorial gene‐environment interactions are likely to be a generic mechanism involved in the majority of cases of mental illness, which is only partially tapped by existing gene‐environment studies. Future research may cut across psychiatric disorders and address poly‐causation by considering multiple genetic and environmental measures across the life course with a specific focus on the first two decades of life. Integrative analyses of poly‐causation including gene‐environment and environment‐environment interactions can realize the potential for discovering causal types and mechanisms that are likely to generate new preventive and therapeutic tools.     

The genetic architecture of behavioral traits in a spider

The existence of consistent individual differences in behavior has been shown in a number of species, and several studies have found observable sex differences in these behaviors, yet their evolutionary implications remain unclear. Understanding the evolutionary dynamics of behavioral traits requires knowledge of their genetic architectures and whether this architecture differs between the sexes. We conducted a quantitative genetic study in a sexually size‐dimorphic spider, Larinioides sclopetarius, which exhibits sex differences in adult lifestyles. We observed pedigreed spiders for aggression, activity, exploration, and boldness and used animal models to disentangle genetic and environmental influences on these behaviors. We detected trends toward (i) higher additive genetic variances in aggression, activity, and exploration in males than females, and (ii) difference in variances due to common environment/maternal effects, permanent environment and residual variance in aggression and activity with the first two variances being higher in males for both behaviors. We found no sex differences in the amount of genetic and environmental variance in boldness. The mean heritability estimates of aggression, activity, exploration, and boldness range from 0.039 to 0.222 with no sizeable differences between females and males. We note that the credible intervals of the estimates are large, implying a high degree of uncertainty, which disallow a robust conclusion of sex differences in the quantitative genetic estimates. However, the observed estimates suggest that sex differences in the quantitative genetic architecture of the behaviors cannot be ruled out. Notably, the present study suggests that genetic underpinnings of behaviors may differ between sexes and it thus underscores the importance of taking sex differences into account in quantitative genetic studies.     

The genetic and environmental effects on depressive symptoms among older female twins.

The aim of the present study was to examine the contribution of genetic and environmental factors to depressive symptoms among older women. The participants were 102 monozygotic and 115 dizygotic female twin pairs aged 64 to 76 years. Depressive symptoms were assessed by the Center for the Epidemiologic Studies Depression Scale. The contribution of genetic and environmental effects was estimated for the constructed depressiveness factor and for the subscales which were depressed mood, psychomotor retardation, lack of wellbeing and interpersonal difficulties. Of the variance in depressiveness, shared environmental influences accounted for 39% and nonshared environmental influences 61%. For the subscales, 24% to 62% of the variance was explained by individual, and 13% to 23% by shared, environmental factors. Lack of wellbeing had its own moderate additive genetic effect explaining 30% of the variance. This study showed that in older women predominantly environmental factors underlay individual differences in depressiveness; however, the factors varied to some extent between dimensions measured by the subscales.     

Sex differences in heritability of BMI: a comparative study of results from twin studies in eight countries.

Body mass index (BMI), a simple anthropometric measure, is the most frequently used measure of adiposity and has been instrumental in documenting the worldwide increase in the prevalence of obesity witnessed during the last decades. Although this increase in overweight and obesity is thought to be mainly due to environmental changes, i.e., sedentary lifestyles and high caloric diets, consistent evidence from twin studies demonstrates high heritability and the importance of genetic differences for normal variation in BMI. We analysed self-reported data on BMI from approximately 37,000 complete twin pairs (including opposite sex pairs) aged 20-29 and 30-39 from eight different twin registries participating in the GenomEUtwin project. Quantitative genetic analyses were conducted and sex differences were explored. Variation in BMI was greater for women than for men, and in both sexes was primarily explained by additive genetic variance in all countries. Sex differences in the variance components were consistently significant. Results from analyses of opposite sex pairs also showed evidence of sex-specific genetic effects suggesting there may be some differences between men and women in the genetic factors that influence variation in BMI. These results encourage the continued search for genes of importance to the body composition and the development of obesity. Furthermore, they suggest that strategies to identify predisposing genes may benefit from taking into account potential sex specific effects.     

Cytokine production by leukocytes of military personnel with depressive symptoms after deployment to a combat-zone: a prospective, longitudinal study

Major depressive disorder (MDD) is frequently diagnosed in military personnel returning from deployment. Literature suggests that MDD is associated with a pro-inflammatory state. To the best of our knowledge, no prospective, longitudinal studies on the association between development of depressive symptomatology and cytokine production by peripheral blood leukocytes have been published. The aim of this study was to investigate whether the presence of depressive symptomatology six months after military deployment is associated with the capacity to produce cytokines, as assessed before and after deployment. 1023 military personnel were included before deployment. Depressive symptoms and LPS- and T-cell mitogen-induced production of 16 cytokines and chemokines in whole blood cultures were measured before (T0), 1 (T1), and 6 (T2) months after return from deployment. Exploratory structural equation modeling (ESEM) was used for data reduction into cytokine patterns. Multiple group latent growth modeling was used to investigate differences in the longitudinal course of cytokine production between individuals with (n = 68) and without (n = 665) depressive symptoms at T2. Individuals with depressive symptoms after deployment showed higher T-cell cytokine production before deployment. Moreover, pre-deployment T-cell cytokine production significantly predicted the presence of depressive symptomatology 6 months after return. There was an increase in T-cell cytokine production over time, but this increase was significantly smaller in individuals developing depressive symptoms. T-cell chemokine and LPS-induced innate cytokine production decreased over time and were not associated with depressive symptoms. These results indicate that increased T-cell mitogen-induced cytokine production before deployment may be a vulnerability factor for development of depressive symptomatology in response to deployment to a combat-zone. In addition, deployment to a combat-zone affects the capacity of T-cells and monocytes to produce cytokines and chemokines until at least 6 months after return.     

Sex differences in claimed and behavioral self-handicapping and ADHD symptomatology in emerging adults

Although the research is clear that boys with ADHD have higher symptomatology and impairment than girls with ADHD, for adults the research is mixed. Some studies suggest no sex differences, whereas others suggest that women might have higher symptomatology and impairment. The present study examined sex differences in ADHD symptomatology and impairment, and the possible role of claimed and behavioral self-handicapping as an explanation for any differences. Claimed self-handicapping (CSH) involves reports of performance-inhibiting conditions, whereas behavioral self-handicapping (BSH) involves reporting more objective, intentional acts that could undermine performance. College students (N = 699) completed an online study. Sex differences were found for hyperactivity such that women reported higher levels, but not for inattention or impairment. The test of the indirect effect of sex through CSH was significant, suggesting that higher levels of CSH in women were associated with elevated ADHD symptoms and impairment. The test of the indirect effect of sex through BSH was also significant, suggesting that higher levels of BSH in men are associated with elevated symptoms of ADHD and impairment. These data extend the literature by suggesting that self-handicapping might at least partially explain differential self-reporting of ADHD symptoms and impairment in emerging adults across the sexes.     

Effects of Heritability,Shared Environment,and Nonshared Intrauterine Conditions on Child and Adolescent BMI

Heritability studies of BMI, based upon twin samples, have identified genetic and shared environmental components of BMI, but have been largely silent about the nonshared environmental factors. Intrauterine factors have been identified as having significant long‐term effects on BMI and may be a critical source of nonshared environmental influence. Extant studies based on samples of either unrelated individuals or twins cannot separate the effects of genetics, shared environments, and nonshared intrauterine conditions because the one lacks variation in the degree of relatedness and the other has insufficient variation in intrauterine conditions. This study improves upon these prior studies by using a large, sibling‐based sample to examine heritability, shared environmental, and nonshared intrauterine influences on BMI during two age periods in childhood (6–8 years; 12–14 years). The primary interest was in determining the effects of the intrauterine environment on BMI as a component of the nonshared environment and in determining whether there were sex‐specific differences in heritability and/or in the intrauterine factors. These were estimated using regression‐based techniques introduced by DeFries and Fulker. Heritability of BMI was estimated to be 0.20–0.28 at 6–8 years and 0.46–0.61 at 12–14 years. Differences in heritability were found at 12–14 years between same‐sex as compared to mixed‐sex pairs. The shared environmental effect was significant at 6–8 years but insignificant at 12–14 years. Differences in birth weight were significant in all groups at 6–8 years suggesting long‐term effects of the nonshared intrauterine environment; at 12–14 years, birth weight was no longer significant for girls.     

Mood rhythmicity is associated with depressive symptoms and caffeinated drinks consumption in South American young adults

Among the factors that contribute to the onset and maintenance of depressive disorders, rhythmicity of symptoms and consumption of caffeine have recently gained attention. The current study aimed to examine the differential rhythmicity of relevant variables in a sample of young participants, considering the presence of depressive symptomatology and the frequency of caffeinated drinks consumption. A significant 24-hour differential rhythmicity of mood, cognitive and physiological variables was found indicating an evening peak pattern in the participants with depressive symptoms. Interestingly, caffeinated drinks consumption was differentially associated with self-perceived peaks, according to the presence of depressive symptomatology. Our findings are among the first reports about the potential association of the 24-hours rhythmicity of relevant mood-related variables, depressive symptoms, and caffeine intake. These results support the view that the identification of risk factors for depression, and the application of novel measurements and analysis methods in the development of new preventive strategies should be a public health priority.     

Stressful life events and depression among adolescent twin pairs

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.     

Heritability of adult body height: a comparative study of twin cohorts in eight countries.

A major component of variation in body height is due to genetic differences, but environmental factors have a substantial contributory effect. In this study we aimed to analyse whether the genetic architecture of body height varies between affluent western societies. We analysed twin data from eight countries comprising 30,111 complete twin pairs by using the univariate genetic model of the Mx statistical package. Body height and zygosity were self-reported in seven populations and measured directly in one population. We found that there was substantial variation in mean body height between countries; body height was least in Italy (177 cm in men and 163 cm in women) and greatest in the Netherlands (184 cm and 171 cm, respectively). In men there was no corresponding variation in heritability of body height, heritability estimates ranging from 0.87 to 0.93 in populations under an additive genes/unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well or better, heritability ranged from 0.89 to 0.93. This difference between the sexes was mainly due to the effect of the shared environmental component of variance, which appears to be more important among women than among men in our study populations. Our results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men.     

Sex Differences in Genetic Architecture of Complex Phenotypes?

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.     

The importance of context to the genetic architecture of diabetes-related traits is revealed in a genome-wide scan of a LG/J?��?SM/J murine model

Variations in diabetic phenotypes are caused by complex interactions of genetic effects, environmental factors, and the interplay between the two. We tease apart these complex interactions by examining genome-wide genetic and epigenetic effects on diabetes-related traits among different sex, diet, and sex-by-diet cohorts in a Mus musculus model. We conducted a genome-wide scan for quantitative trait loci that affect serum glucose and insulin levels and response to glucose stress in an F₁₆ Advanced Intercross Line of the LG/J and SM/J intercross (Wustl:LG,SM-G16). Half of each sibship was fed a high-fat diet and half was fed a relatively low-fat diet. Context-dependent genetic (additive and dominance) and epigenetic (parent-of-origin imprinting) effects were characterized by partitioning animals into sex, diet, and sex-by-diet cohorts. We found that different cohorts often have unique genetic effects at the same loci, and that genetic signals can be masked or erroneously assigned to specific cohorts if they are not considered individually. Our data demonstrate that the effects of genes on complex trait variation are highly context-dependent and that the same genomic sequence can affect traits differently depending on an individual??s sex and/or dietary environment. Our results have important implications for studies of complex traits in humans.     

Heritability of blood pressure increases during mental stress.

We studied the influence of mental stress on the contributions of genes and environment to individual variation in systolic (SBP) and diastolic (DBP) blood pressure by structural equation modelling in 320 adolescent male and female twins. Blood pressure data were collected during rest and during a reaction time and a mental arithmetic task. Univariate analyses of SBP and DBP showed familial aggregation for blood pressure. A genetic explanation for this resemblance was most likely, although during rest conditions a model that attributed familial resemblance to shared environmental factors, also fitted the data. There was no evidence for sex differences in heritabilities. Multivariate analyses showed significant heterogeneity between sexes for the intercorrelations of the blood pressure data measured under different rest and task conditions. Multivariate genetic analyses were therefore carried out separately in males and females. For SBP and DBP in females and for SBP in males an increase in heritabilities was seen for blood pressure measured during stress, as compared to rest measurements. The influence of shared environmental factors decreased during stress. For DBP in males no significant contributions of shared environment were found. The multivariate analyses indicated that the same genetic and environmental influences are expressed during rest and stress conditions.     

A multivariate twin study of hippocampal volume, self-esteem and well-being in middle-aged men

Self-esteem and well-being are important for successful aging, and some evidence suggests that self-esteem and well-being are associated with hippocampal volume, cognition and stress responsivity. Whereas most of this evidence is based on studies on older adults, we investigated self-esteem, well-being and hippocampal volume in 474 male middle-aged twins. Self-esteem was significantly positively correlated with hippocampal volume (0.09, P = 0.03 for left hippocampus, 0.10, P = 0.04 for right). Correlations for well-being were not significant (Ps > 0.05). There were strong phenotypic correlations between self-esteem and well-being (0.72, P < 0.001) and between left and right hippocampal volume (0.72, P < 0.001). In multivariate genetic analyses, a two-factor additive genetic and unique environmental (AE) model with well-being and self-esteem on one factor and left and right hippocampal volumes on the other factor fits the data better than Cholesky, independent pathway or common pathway models. The correlation between the two genetic factors was 0.12 (P = 0.03); the correlation between the environmental factors was 0.09 (P > 0.05). Our results indicate that largely different genetic and environmental factors underlie self-esteem and well-being on one hand and hippocampal volume on the other.     

Between‐sex genetic covariance constrains the evolution of sexual dimorphism in Drosophila melanogaster

Males and females share much of their genome, and as a result, intralocus sexual conflict is generated when selection on a shared trait differs between the sexes. This conflict can be partially or entirely resolved via the evolution of sex‐specific genetic variation that allows each sex to approach, or possibly achieve, its optimum phenotype, thereby generating sexual dimorphism. However, shared genetic variation between the sexes can impose constraints on the independent expression of a shared trait in males and females, hindering the evolution of sexual dimorphism. Here, we examine genetic constraints on the evolution of sexual dimorphism in Drosophila melanogaster cuticular hydrocarbon (CHC) expression. We use the extended G matrix, which includes the between‐sex genetic covariances that constitute the B matrix, to compare genetic constraints on two sets of CHC traits that differ in the extent of their sexual dimorphism. We find significant genetic constraints on the evolution of further dimorphism in the least dimorphic traits, but no such constraints for the most dimorphic traits. We also show that the genetic constraints on the least dimorphic CHCs are asymmetrical between the sexes. Our results suggest that there is evidence both for resolved and ongoing sexual conflict in D. melanogaster CHC profiles.     

Negative emotionality, depressive symptoms and cortisol diurnal rhythms: analysis of a community sample of middle-aged males

Prior research suggests that individuals with particular personality traits, like negative emotionality, are at greater risk for adverse health outcomes. Despite bivariate associations between negative emotionality, depressive symptoms and the hypothalamic pituitary adrenal axis (HPA axis), few studies have sought to understand the biological pathways through which negative emotionality, depressive symptomatology and cortisol—one of the primary hormonal products of the HPA axis—are associated. The present study explored whether negative emotionality influenced cortisol dysregulation through current depressive symptomatology and whether negative emotionality served as a moderator of the relationship between depressive symptoms and cortisol. In the community-based Vietnam Era Twin Study of Aging, 783 male twins completed two days of cortisol saliva sampling in their natural environments. Three measures of cortisol were analyzed: waking levels, the cortisol awakening response, and the peak to bed slope. Depressive symptoms significantly mediated the associations between negative emotionality and the peak to bed slope. A 2-way interaction between depressive symptoms and negative emotionality was significant for the peak to bed slope and for waking levels of cortisol. Exploration of the interactions illustrated that depressive symptoms only affected cortisol slopes at average or high levels of negative emotionality and only affected waking levels at low levels of negative emotionality. Negative emotionality and depressive symptoms were not related to the cortisol awakening response. This is the first study to find indirect associations between negative emotionality and peak to bed cortisol slopes through depressive symptoms. These findings illustrate the complex interplay between personality characteristics, depressive symptoms and different indices of the cortisol diurnal rhythm.     

Investigating the genetic and environmental structure of Cloninger's personality dimensions in adolescence.

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.     

Genetic influences in self-reported symptoms of obstructive sleep apnoea and restless legs: a twin study.

Sleep disorders, such as obstructive sleep apnoea (OSA) and restless legs syndrome (RLS), are very common. The relative importance of genetic and nongenetic (environmental) influences on the symptomatology of these conditions has not been well studied. This study uses the twin design to examine this by evaluating OSA and RLS symptoms in monozygotic (MZ) and dizygotic (DZ) twins. Six thousand six hundred unselected female twin pairs, identified from a national volunteer twin register, were asked to complete a medical questionnaire. This questionnaire included questions on OSA and RLS symptoms, as well as questions on subject demographics, past medical history, smoking history and menopausal status. Responses were obtained from 4503 individuals (68% response rate). A total of 1937 twin pairs were evaluable: 933 MZ pairs (mean [range] age 51 [20-76] years) and 1004 DZ pairs (age 51 [20-80] years). Concordance rates were higher for MZ than DZ twins for OSA and RLS symptoms. Multifactorial liability threshold modeling suggests that additive genetic effects combined with unique environmental factors provide the best model for OSA and RLS symptoms. Heritability was estimated to be 52% (95% confidence interval 36% to 68%) for disruptive snoring, 48% (37% to 58%) for daytime sleepiness, 54% (44% to 63%) for restless legs, and 60% (51% to 69%) for legs jerking. These estimates dropped only slightly after adjustment for potential confounding influences on the symptoms of snoring and daytime sleepiness. These results suggest a substantial genetic contribution to the symptomatology of OSA and RLS. More research is needed to identify the genes responsible, and may ultimately lead to new therapies.