Heritability of cerebellar subregion volumes in adolescent and young adult twins.

Twin studies have found gross cerebellar volume to be highly heritable. However, whether fine-grained regional volumes within the cerebellum are similarly heritable is still being determined. Anatomical MRI scans from two independent datasets (QTIM: Queensland Twin IMaging, N = 798, mean age 22.1 years; QTAB: Queensland Twin Adolescent Brain, N = 396, mean age 11.3 years) were combined with an optimised and automated cerebellum parcellation algorithm to segment and measure 28 cerebellar regions. We show that the heritability of regional volumetric measures varies widely across the cerebellum ( h 2 $$ {h}^2 $$ 47%-91%). Additionally, the good to excellent test-retest reliability for a subsample of QTIM participants suggests that non-genetic variance in cerebellar volumes is due primarily to unique environmental influences rather than measurement error. We also show a consistent pattern of strong associations between the volumes of homologous left and right hemisphere regions. Associations were predominantly driven by genetic effects shared between lobules, with only sparse contributions from environmental effects. These findings are consistent with similar studies of the cerebrum and provide a first approximation of the upper bound of heritability detectable by genome-wide association studies.

A Genetically Informed Study of the Association Between Perceived Stress and Loneliness.

Although research shows a strong positive association between perceived stress and loneliness, the genetic and environmental etiology underlying their association remains unknown. People with a genetic predisposition to perceived stress, for example, may be more prone to feeling lonely and vice versa. Conversely, unique factors in people's lives may explain differences in perceived stress levels that, in turn, affect feelings of loneliness. We tested whether genetic factors, environmental factors, or both account for the association between perceived stress and loneliness. Participants were 3,066 individual twins (nFemale = 2,154, 70.3%) from the Washington State Twin Registry who completed a survey during April-May, 2020. Structural equation modeling was used to analyze the item-level perceived stress and loneliness measures. The correlation between latent perceived stress and latent loneliness was .68. Genetic and nonshared environmental variance components underlying perceived stress accounted for 3.71% and 23.26% of the total variance in loneliness, respectively. The genetic correlation between loneliness and perceived stress was .45 and did not differ significantly between men and women. The nonshared environmental correlation was .54 and also did not differ between men and women. Findings suggest that holding constant the strong genetic association between perceived stress and loneliness, unique life experiences underlying people's perceived stress account for individual differences in loneliness.

Calculating Within-Pair Difference Scores in the Co-twin Control Design. Effects of Alternative Strategies.

Co-twin studies are an elegant and powerful design that allows controlling for the effect of confounding variables, including genetic and a range of environmental factors. There are several approaches to carry out this design. One of the methods commonly used, when contrasting continuous variables, is to calculate difference scores between members of a twin pair on two associated variables, in order to analyse the covariation of such differences. However, information regarding whether and how the different ways of estimating within-pair difference scores may impact the results is scant. This study aimed to compare the results obtained by different methods of data transformation when performing a co-twin study and test how the magnitude of the association changes using each of those approaches. Data was simulated using a direction of causation model and by fixing the effect size of causal path to low, medium, and high values. Within-pair difference scores were calculated as relative scores for diverse within-pair ordering conditions or absolute scores. Pearson's correlations using relative difference scores vary across the established scenarios (how twins were ordered within pairs) and these discrepancies become larger as the within-twin correlation increases. Absolute difference scores tended to produce the lowest correlation in every condition. Our results show that both using absolute difference scores or ordering twins within pairs, may produce an artificial decrease in the magnitude of the studied association, obscuring the ability to detect patterns compatible with causation, which could lead to discrepancies across studies and erroneous conclusions.

Genotype-Environment Interaction in ADHD: Genetic Predisposition Determines the Extent to Which Environmental Influences Explain Variability in the Symptom Dimensions Hyperactivity and Inattention.

Although earlier research has shown that individual differences on the spectrum of attention deficit hyperactivity disorder (ADHD) are highly heritable, emerging evidence suggests that symptoms are associated with complex interactions between genes and environmental influences. This study investigated whether a genetic predisposition [Note that the term 'genetic predisposition' was used in this manuscript to refer to an estimate based on twin modeling (an individual's score on the latent trait that resembles additive genetic influences) in the particular population being examined.] for the symptom dimensions hyperactivity and inattention determines the extent to which unique-environmental influences explain variability in these symptoms. To this purpose, we analysed a sample drawn from the Twins Early Development Study (TEDS) that consisted of item-level scores of 2168 16-year-old twin pairs who completed both the Strengths and Difficulties Questionnaire (SDQ; Goodman, in J Child Psychol Psychiatry 38:581-586, 1997) and the Strength and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN; Swanson, in Paper presented at the meeting of the American Psychological Association, Los Angeles, 1981) questionnaire. To maximize the psychometric information to measure ADHD symptoms, psychometric analyses were performed to investigate whether the items from the two questionnaires could be combined to form two longer subscales. In the estimation of genotype-environment interaction, we corrected for error variance heterogeneity in the measurement of ADHD symptoms through the application of item response theory (IRT) measurement models. A positive interaction was found for both hyperactivity (e.g., [Formula: see text] = 2.20 with 95% highest posterior density interval equal to [1.79;2.65] and effect size equal to 3.00) and inattention (e.g., [Formula: see text] = 2.16 with 95% highest posterior density interval equal to [1.56;2.79] and effect size equal to 3.07). These results indicate that unique-environmental influences were more important in creating individual differences in both hyperactivity and inattention for twins with a genetic predisposition for these symptoms than for twins without such a predisposition.

Age effects on autism heritability and etiological stability of autistic traits.

BACKGROUND: Autism and autistic traits onset in childhood but persist into adulthood. Little is known about how genetic and environmental factors influence autism and autistic traits into adulthood. We aimed to determine age effects on the heritability of clinically diagnosed autism and the etiological stability of autistic traits from childhood to adulthood using twin methods. METHODS: From 23,849 twin pairs in the Swedish Twin Register born between 1959 and 2010, we identified 485 individuals (1.01%, 31.5% female) with a clinical autism diagnosis. We estimated and compared the relative contribution of genetic, shared, and nonshared environmental influences to autism in childhood and adulthood. We further used multivariate twin analysis with four measurement points among 1,348 twin pairs in the longitudinal Twin Study of Child and Adolescent Development to assess the phenotypic and etiological stability of autistic traits - measured with three scales from the Child Behavior Checklist - from childhood to adulthood. RESULTS: Autism heritability was comparable from childhood, (96% [95% CI, 76-99%]) to adulthood (87% [67-96%]). Autistic traits were moderately stable (phenotypic correlation = 0.35-0.61) from childhood to adulthood, and their heritability varied between 52 and 71%. We observed stable as well as newly emerging genetic influences on autistic traits from ages 8-9 to 19-20, and unique nonshared environmental influences at each age. CONCLUSIONS: Genetic factors are important for autism and autistic traits in adulthood and separate genetic studies in adults are warranted.

Genetic confounding in the association of early motor development with childhood and adolescent exercise behavior.

INTRODUCTION: Early motor development has been found to be a predictor of exercise behavior in children and adolescents, but whether this reflects a causal effect or confounding by genetic or shared environmental factors remains to be established. METHODS: For 20,911 complete twin pairs from the Netherlands Twin Register a motor development score was obtained from maternal reports on the timing of five motor milestones. During a 12-year follow-up, subsamples of the mothers reported on the twins' ability to perform seven gross motor skills ability (N = 17,189 pairs), and weekly minutes of total metabolic equivalents of task (MET) spent on sports and exercise activities at age 7 (N = 3632 pairs), age 10 (N = 3735 pairs), age 12 (N = 7043 pairs), and age 14 (N = 3990 pairs). Multivariate phenotypic and genetic regression analyses were used to establish the predictive strength of the two motor development traits for future exercise behavior, the contribution of genetic and shared environmental factors to the variance in all traits, and the contribution of familial confounding to the phenotypic prediction. RESULTS: Significant heritability (h2) and shared environmental (c2) effects were found for early motor development in boys and girls (h2 = 43-65%; c2 = 16-48%). For exercise behavior, genetic influences increased with age (boys: h2age7 = 22% to h2age14 = 51%; girls: h2age7 = 3% to h2age14 = 18%) paired to a parallel decrease in the influence of the shared environment (boys: c2age7 = 68% to c2age14 = 19%; girls: c2age7 = 80% to c2age14 = 48%). Early motor development explained 4.3% (p < 0.001) of the variance in future exercise behavior in boys but only 1.9% (p < 0.001) in girls. If the effect in boys was due to a causal effect of motor development on exercise behavior, all of the factors influencing motor development would, through the causal chain, also influence future exercise behavior. Instead, only the genetic parts of the regression of exercise behavior on motor development were significant. Shared and unique environmental parts of the regression were largely non-significant, which is at odds with the causal hypothesis. CONCLUSION: No support was found for a direct causal effect in the association between rapid early motor development on future exercise behavior. In boys, early motor development appears to be an expression of the same genetic factors that underlie the heritability of childhood and early adolescent exercise behavior.

Genetic and Environmental Influences on Perceived Stress in South Korean Twins.

Researchers have proposed that culture significantly influences perceived stress (PS). To date, however, twin studies on PS have been conducted mostly in western, individualistic cultures, which demonstrate that PS due to controllable (personal) life events is more heritable than PS due to uncontrollable (network) life events. This study aimed to investigate genetic and environmental influences on PS in South Korean twins. South Korea practices a dominant collectivist culture. In total, 1372 twin individuals (mean age = 22.4 ± 2.5 years) completed an online survey on PS, which consisted of the scales, Friendship, Academic Stress, Future Career, Family Conflicts, and Family Financial Difficulties (FFD). Friendship, Academic Stress, and Future Career can be considered PS due to personal life events, and Family Conflict and FFD, PS due to network life events. The general sex-limitation model-fitting analysis revealed the absence of qualitative or quantitative sex differences in genetic and environmental influences. Specifically, additive genetic influences were predominant for Friendship (63%), Academic Stress (67%), and Future Career (57%) for both sexes, with the remaining variance attributable to nonshared environmental influences. In contrast, shared environmental influences were largest for Family Conflict (47% for both genders) and FFD (64% for males, 63% for females) with no significant genetic effects. Despite known cultural differences in the means and variances of PS, South Korean twins exhibited significant genetic effects in PS due to personal life events and large shared environmental effects in PS due to network life events, which is similar to western samples.

Genetics and sleep bruxism: a systematic review and meta-analysis of studies with twins.

OBJECTIVE: To systematically review the literature regarding the concordance of sleep bruxism (SB) between monozygotic (MZ) and dizygotic (DZ) twins. METHODS: The registration for this systematic review was accomplished in the International Prospective Register of Systematic Reviews (PROSPERO, No. CRD42021251751). As of July 2022, four databases were searched, including PubMed, Scopus, Embase, and Web of Science, as well as the grey literature in Google Scholar and OpenGrey. Observational studies evaluating SB in MZ and DZ twins of any age and sex were included. For the evaluation of the risk of bias, the Joanna Briggs checklist was utilized. The certainty of evidence was assessed via the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Pooled and subgroup meta-analyses were performed to estimate concordance of SB ​​between twins (p < 0.05). RESULTS: In total, 3,155 records were identified. In the qualitative analysis, eleven studies were included; of these, seven were included in the meta-analysis. The majority of the articles exhibited a low risk of bias (63.6%). Greater SB concordance was observed between MZ twins than between DZ twins in the analysis of general concordance (OR = 1.47; 95% CI = 1.07-2.02) and also positive concordance (OR = 1.53; 95% CI = 1.29-1.81). Within the subgroup analyses, the significance of the findings remained only for the reported/self-reported SB regarding general concordance (OR = 1.44; 95% CI = 1.07-1.95) and positive concordance (OR = 1.55; 95% CI = 1.28-1.88). Low certainty of the evidence was observed for the general concordance analysis, while moderate certainty was observed for the positive concordance. CONCLUSION: There was a higher concordance of SB in MZ twins compared to DZ twins, indicating a possible genetic influence on the condition's occurrence.

The role of familial factors and neuroticism in the association between exposure to offensive behaviors at work and long-term sickness absence due to common mental disorders - a prospective twin study.

OBJECTIVES: The aim of this study was to investigate associations between exposure to work-related violence/threats and harassment, and future sickness absence (SA) due to common mental disorders (CMDs), taking familial factors (shared genetics and early-life environment) and neuroticism into account. METHODS: The study sample included 8795 twin individuals from the Swedish Twin Project of Disability Pension and Sickness Absence (STODS), including survey data from the Study of Twin Adults: Genes and Environment (STAGE). Self-reported work-related violence and/or threats as well as work-related harassment (including bullying) and national register data on SA due to CMDs were analyzed using standard logistic regression, and conditional logistic regression among complete twin pairs discordant on exposures. Individuals were followed for a maximum of 13 years. Interactions between neuroticism and exposures were assessed using both multiplicative and additive interaction analyses. RESULTS: Exposure to work-related violence/threats was associated with higher odds of SA due to CMDs when adjusting for age, sex, marital status, children, education, type of living area, work characteristics, and symptoms of depression and burnout (OR 2.11, 95% CI 1.52-2.95). Higher odds of SA due to CMDs were also found for exposure to harassment (OR 1.52, 95% CI 1.10-2.11) and a combined indicator of exposure to violence/threats and/or harassment (OR 1.98, 95% CI 1.52-2.59), compared with the unexposed. Analyses of twins discordant on exposure, using the unexposed co-twin as reference, showed reduced ORs. These ORs were still elevated but no longer statistically significant, potentially due to a lack of statistical power. No multiplicative interaction was found between neuroticism and exposure to work-related violence/threats, or harassment. However, a statistically significant additive interaction was found between neuroticism and exposure to violence/threats, indicating higher odds of SA due to CMDs in the group scoring lower on neuroticism. CONCLUSIONS: Exposure to work-related offensive behaviors was associated with SA due to CMDs. However, the results indicated that these associations may be partly confounded by familial factors. In addition, an interaction between exposure and neuroticism was suggested. Thus, when possible, future studies investigating associations and causality between offensive behaviors at work and mental health-related outcomes, should consider familial factors and neuroticism.

Longitudinal multi-omics study reveals common etiology underlying association between plasma proteome and BMI trajectories in adolescent and young adult twins.

BACKGROUND: The influence of genetics and environment on the association of the plasma proteome with body mass index (BMI) and changes in BMI remains underexplored, and the links to other omics in these associations remain to be investigated. We characterized protein-BMI trajectory associations in adolescents and adults and how these connect to other omics layers. METHODS: Our study included two cohorts of longitudinally followed twins: FinnTwin12 (N = 651) and the Netherlands Twin Register (NTR) (N = 665). Follow-up comprised 4 BMI measurements over approximately 6 (NTR: 23-27 years old) to 10 years (FinnTwin12: 12-22 years old), with omics data collected at the last BMI measurement. BMI changes were calculated in latent growth curve models. Mixed-effects models were used to quantify the associations between the abundance of 439 plasma proteins with BMI at blood sampling and changes in BMI. In FinnTwin12, the sources of genetic and environmental variation underlying the protein abundances were quantified by twin models, as were the associations of proteins with BMI and BMI changes. In NTR, we investigated the association of gene expression of genes encoding proteins identified in FinnTwin12 with BMI and changes in BMI. We linked identified proteins and their coding genes to plasma metabolites and polygenic risk scores (PRS) applying mixed-effects models and correlation networks. RESULTS: We identified 66 and 14 proteins associated with BMI at blood sampling and changes in BMI, respectively. The average heritability of these proteins was 35%. Of the 66 BMI-protein associations, 43 and 12 showed genetic and environmental correlations, respectively, including 8 proteins showing both. Similarly, we observed 7 and 3 genetic and environmental correlations between changes in BMI and protein abundance, respectively. S100A8 gene expression was associated with BMI at blood sampling, and the PRG4 and CFI genes were associated with BMI changes. Proteins showed strong connections with metabolites and PRSs, but we observed no multi-omics connections among gene expression and other omics layers. CONCLUSIONS: Associations between the proteome and BMI trajectories are characterized by shared genetic, environmental, and metabolic etiologies. We observed few gene-protein pairs associated with BMI or changes in BMI at the proteome and transcriptome levels.

Differential methylation patterns from clusters associated with glucose metabolism: evidence from a Shanghai twin study.

Aim: To assess the associations between genome-wide DNA methylation (DNAm) and glucose metabolism among a Chinese population, in particular the multisite correlation. Materials & methods: Epigenome-wide associations with fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were analyzed among 100 Shanghai monozygotic (MZ) twin pairs using the Infinium HumanMethylationEPIC v2.0 BeadChip. We conducted a Pearson's correlation test, hierarchical cluster and pairwise analysis to examine the differential methylation patterns from clusters. Results: Cg01358804 (TXNIP) was identified as the most significant site associated with FPG and HbA1c. Two clusters with hypermethylated and hypomethylated patterns were observed for both FPG and HbA1c. Conclusion: Differential methylation patterns from clusters may provide new clues for epigenetic changes and biological mechanisms in glucose metabolism.

Twin Study: The Factors Affecting the Serum LDL-C and HDL-C Levels and an RNA-Seq Analysis in Mononuclear Cells in Monozygotic Twins.

AIM: A twin study is a valuable tool for elucidating the acquired factors against lifestyle diseases such as dyslipidemia, diabetes mellitus, and obesity. We aimed 1. to investigate the factors that affect low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in monozygotic (MZ) twins, and 2. to identify genes which expression levels changed in pairs with large differences in LDL-C or HDL-C levels. METHODS: The registered database at the Center for Twin Research, Osaka University, containing 263 pairs of MZ twins, was analyzed. 1. The effects of smoking, exercise, nutritional factors, and anthropometric and biochemical parameters on LDL-C or HDL-C levels were examined in MZ twins. 2. RNA sequencing in the peripheral blood mononuclear cells of 59 pairs was analyzed for large differences of LDL-C or HDL-C groups. RESULTS: 1. The ΔLDL-C levels were significantly associated with an older age, the ΔTG levels, and ΔBMI. ΔHDL-C levels were associated with the ΔBMI, ΔTG, ΔTP, and ΔLDL-C levels. The HDL-C levels were affected by smoking and exercise habits. The intakes of cholesterol and saturated fatty acids were not associated with the LDL-C or HDL-C levels. 2. An RNA sequencing analysis revealed that the expression of genes related to the TLR4 and IFNG pathways was suppressed in accordance with the HDL-C levels in the larger ΔHDL-C group among the 59 pairs. CONCLUSION: We identified the factors affecting the LDL-C or HDL-C levels in monozygotic twins. In addition, some types of inflammatory gene expression in peripheral blood mononuclear cells were suppressed in accordance with the HDL-C levels, thus suggesting the importance of weight management and exercise habits in addition to dietary instructions to control the LDL-C or HDL-C levels.

Basic or Adaptation: The Assessment and Heritability of a Brief Measure of Agency.

The interpersonal circumplex describes two major axes of personality that guide much of social behavior. Agency, one half of the interpersonal circumplex, refers to relatively stable behavioral patterns that center on self-focused dominance and assertiveness. Past empirical work on agency tends to treat the dimension as a characteristic adaptation, rather than a basic component of personality, in part due to the relatively large gender difference in agency with masculine individuals tending to behave more agentic. However, the psychometric overlap between agency and the most closely linked big five dimension, extraversion, is not well-established, and no behavior genetic work has documented evidence concerning the role of genetic and environmental influences. It is unclear whether agency is more similar to a personality trait, with no evidence of shared environmental influence and moderate heritability, or a characteristic adaptation, with some evidence for shared environmental influence and possibly lower heritability. We used the Midlife Development in the United States study to examine agency, big five, and generativity with replication and robustness check (Nnon-twins = 5,194; Ntwins = 1,914; NMilwaukee = 592). Results indicated that agency was higher in men (d = -.24), moderately heritable (44.4%), strongly correlated with extraversion (r = .51), moderately correlated with generativity (r = .36), and that approximately 40% of the variance in agency was shared with the big five. Agency also changed strongly with extraversion and openness, but less so generativity. Altogether, these results indicate that agency functions similar to other basic personality dimensions but is not clearly a dispositional trait.

Twin study: genotype-dependent epigenetic factors affecting free thyroxine levels in the normal range.

Aim: To explore the clinical application of DNA methylation affecting thyroid function, we evaluated the association of DNA methylation with free thyroxine (FT4) and TSH measurements in monozygotic twins. Materials & methods: Discordant pairs for FT4 or TSH levels were examined for the relationship between the within-pair difference of each measurement and the DNA methylation levels using epigenome-wide association studies. The contribution of polymorphisms to the methylation sensitivity was also examined. Results: We found two CpG sites significantly associated with FT4 levels, and also some CpG sites showing significant differences in their methylation levels within FT4-discordant pairs depending on the polymorphism in EPHB2. Conclusion: The FT4 level may be associated with a combination of methylation and polymorphisms in the EPHB2 gene.

Continuity and change of genetic and environmental influences on reading and reading-related neurocognitive skills: A systematic review of longitudinal twin studies.

Learning to read is a dynamic and cumulative process beginning from birth and continuing through the school years. Empirical data showed a decrease of additive genetic (A) and shared environmental (C) components and an increase of non-shared environmental (E) components from preschool to middle school. However, our understanding of the aetiology of continuity and change of reading skills across this developmental period is limited. Following the PRISMA guidelines, we reviewed the results of behavioral genetic research on reading-related neurocognitive skills of 13 longitudinal twin and adoptive sibling studies spanning from preschool/kindergarten to middle/high school. Our findings suggested that continuity was mainly explained by A components throughout the study periods, and, although to a lesser extent and less consistently, by C components during the early years; change was explained by new E components throughout the years, and also by new A components in the early years. As we are interested in models relevant to traits with early onset during development, it is crucial to deepen the investigation of how developmental time can moderate the genetic and environmental variation.

Genetic and environmental influences on alpha amylase stress reactivity and shared genetic covariation with cortisol.

Salivary alpha amylase (sAA) is a common measure of stress reactivity, primarily reflecting sympathetic nervous system activity. Salivary cortisol is also a reliable, frequently used biomarker of stress and reflects the hypothalamic-pituitary-adrenal (HPA) axis response. This study examined heritability across varying metrics of sAA in response to a social evaluative stressor, the Trier Social Stress Test (TSST). The goal of this study was to estimate genetic and environmental influences on measurements of sAA stress reactivity. Moreover, we evaluated the shared genetic covariation between sAA and cortisol. Participants included twins aged 15-20 years (54% female). We measured alpha amylase and cortisol reactivity to the TSST via serial salivary cortisol samples collected pre- and post-TSST. Modest to moderate heritability estimates (11-64%) were observed across measures purported to capture alpha amylase stress reactivity (peak, area under the curve, baseline-to-peak change). Findings also indicate that sAA baseline and peak are primarily influenced by a shared genetic factor. There was no evidence of shared genetic influences between sAA and cortisol. These findings suggest the genetic control of the HPA and Sympathetic Adreno-Medullar axis are genetically independent of one another despite both playing a role in response to stressors.

The breakdown of social looking.

Individual differences in social looking are commonly believed to reflect one single heritable dimension tightly linked to autism. Yet, recent data suggest that in human infants, looking to eyes (rather than mouth) and preference for faces (versus non-social objects) reflect distinct genetic influences, and neither appear to have a clear-cut relation to autism.

Mental disorders and discrimination: A prospective cohort study of young twin pairs in Germany.

Background: Mental disorders and perceived discrimination share common risk factors. The association between having a mental disorder and experiencing discrimination is well-known, but the extent to which familial factors, such as genetic and shared environmental factors, might confound this association, including sex differences in familial confounding, remains unexplored. Aims: We investigated potential unmeasured familial confounding in the association between mental disorders and perceived discrimination using a matched twin study design. Method: We examined data from 2044 same-sex twin pairs (n = 4088) aged 16-25 years from the German population-based study 'TwinLife'. We applied random-effects logistic regression to within-individual and within-and-between pair models of the association between mental disorder and perceived discrimination, and used likelihood ratio tests (LRTs) to compare these models. Multivariable models were adjusted for body mass index, educational attainment, and life satisfaction. Results: There were 322 (8.1%) participants with a diagnosed mental disorder, and 15% (n = 604) of the cohort reported having experienced discrimination in the previous 12 months. Mental disorder and discrimination were associated in the adjusted within-individual model (adjusted odds ratio = 2.19, 95% confidence interval: 1.42-3.39, P<0.001). However, the within-and-between pair model showed that this association was explained by the within-pair mean (aOR = 4.24, 95% CI: 2.17-8.29, P<0.001) and not the within-pair difference (aOR = 1.26, 95% CI: 0.70-2.28, P = 0.4) of mental disorder. Therefore, this association was mostly explained by familial confounding, which is also supported by the LRTs for the unadjusted and adjusted models (P<0.001 and P = 0.03, respectively). This familial confounding was more prominent for males than females. Conclusions: Our findings show that the association between mental disorder and discrimination is at least partially explained by unmeasured familial factors. Designing family-based healthcare models and incorporating family members in interventions targeted at ameliorating mental ill-health and experiences of discrimination among adolescents may improve efficacy.

Monozygotic twins discordant for depression: An extended network comparison of depressive symptoms, cognitive functions and daily activities.

Monozygotic twins share the same genotype; however, they can be phenotypically discordant on various traits. Studying discordant monozygotic twins allows the investigation of differences in associations between symptoms and psychopathological risk factors, controlled for shared genetic liability. The network approach to psychopathology suggests that depressive symptoms, along with risk and protective factors (e.g., cognition, daily activities), form a complex system of mutually interacting components. We compared monozygotic twins discordant for lifetime depression on their respective extended networks of depressive symptoms, cognitive functions and daily activities (intellectual, physical, social), and evaluated if these networks differ in their associations between variables and in the role of each variable within the network. Regularized partial correlations investigated the networks' composition in 147 monozygotic twin pairs discordant for depression from the Danish Twin Registry. Affected twins had stronger overall associations within their network of depressive symptoms, cognitive functions and daily activities than their unaffected co-twins, while the importance of the network components' associations did not differ between the co-twins. In affected twins, decreased frequency in experiencing happiness had the strongest association with remaining variables (i.e., the most influence in activating other network elements). Also, variables from different groups were significantly associated (e.g., loneliness with delayed memory, pessimism with low social activities, verbal learning with intellectual activities). In unaffected twins, both mood symptoms and cognitive functions were important, but between-groups associations were quasi-absent. These results suggest that external events affecting the ability to feel happiness likely trigger the psychopathological process (depression network activation), independently from the genetic predisposition to depression.

Rapid dynamics of electrophysiological connectome states are heritable.

Time-varying changes in whole-brain connectivity patterns, or connectome state dynamics, are a prominent feature of brain activity with broad functional implications. While infra-slow (<0.1Hz) connectome dynamics have been extensively studied with fMRI, rapid dynamics highly relevant for cognition are poorly understood. Here, we asked whether rapid electrophysiological connectome dynamics constitute subject-specific brain traits and to what extent they are under genetic influence. Using source-localized EEG connectomes during resting-state (N=928, 473 females), we quantified heritability of multivariate (multi-state) features describing temporal or spatial characteristics of connectome dynamics. States switched rapidly every ~60-500ms. Temporal features were heritable, particularly, Fractional Occupancy (in theta, alpha, beta, and gamma bands) and Transition Probability (in theta, alpha, and gamma bands), representing the duration spent in each state and the frequency of state switches, respectively. Genetic effects explained a substantial proportion of phenotypic variance of these features: Fractional Occupancy in beta (44.3%) and gamma (39.8%) bands and Transition Probability in theta (38.4%), alpha (63.3%), beta (22.6%), and gamma (40%) bands. However, we found no evidence for heritability of spatial features, specifically states' Modularity and connectivity pattern. We conclude that genetic effects strongly shape individuals' connectome dynamics at rapid timescales, specifically states' overall occurrence and sequencing.