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Objective: Advanced paternal age (APA) at conception has been linked with autism and schizophrenia in offspring, neurodevelopmental disorders that affect social functioning. The current study explored the effects of paternal age on social development in the general population.Method: We used multilevel growth modeling to investigate APA effects on socioemotional development from early childhood until adolescence, as measured by the Strengths and Difficulties Questionnaire (SDQ) in the Twins Early Development Study (TEDS) sample. We also investigated genetic and environmental underpinnings of the paternal age effects on development, using the Additive genetics, Common environment, unique Environment (ACE) and gene-environment (GxE) models.Results: In the general population, both very young and advanced paternal ages were associated with altered trajectory of social development (intercept: p = .01; slope: p = .03). No other behavioral domain was affected by either young or advanced age at fatherhood, suggesting specificity of paternal age effects. Increased importance of genetic factors in social development was recorded in the offspring of older but not very young fathers, suggesting distinct underpinnings of the paternal age effects at these two extremes.Conclusion: Our findings highlight that the APA-related deficits that lead to autism and schizophrenia are likely continuously distributed in the population. [ABSTRACT FROM AUTHOR]

Background The etiology of Autism Spectrum Disorder ( ASD) has been recently debated due to emerging findings on the importance of shared environmental influences. However, two recent twin studies do not support this and instead re-affirm strong genetic effects on the liability to ASD, a finding consistent with previous reports. This study conducts a systematic review and meta-analysis of all twin studies of ASD published to date and explores the etiology along the continuum of a quantitative measure of ASD. Methods A PubMed Central, Science Direct, Google Scholar, Web of Knowledge structured search conducted online, to identify all twin studies on ASD published to date. Thirteen primary twin studies were identified, seven were included in the meta-analysis by meeting Systematic Recruitment criterion; correction for selection and ascertainment strategies, and applied prevalences were assessed for these studies. In addition, a quantile DF extremes analysis was carried out on Childhood Autism Spectrum Test scores measured in a population sample of 6,413 twin pairs including affected twins. Results The meta-analysis correlations for monozygotic twins ( MZ) were almost perfect at .98 (95% Confidence Interval, .96-.99). The dizygotic ( DZ) correlation, however, was .53 (95% CI .44-.60) when ASD prevalence rate was set at 5% (in line with the Broad Phenotype of ASD) and increased to .67 (95% CI .61-.72) when applying a prevalence rate of 1%. The meta-analytic heritability estimates were substantial: 64-91%. Shared environmental effects became significant as the prevalence rate decreased from 5-1%: 07-35%. The DF analyses show that for the most part, there is no departure from linearity in heritability. Conclusions We demonstrate that: (a) ASD is due to strong genetic effects; (b) shared environmental effects become significant as a function of lower prevalence rate; (c) previously reported significant shared environmental influences are likely a statistical artefact of overinclusion of concordant DZ twins. [ABSTRACT FROM AUTHOR]

The online version of the original article can be found at https://doi.org/10.1007/s10519-022-10114-x. In the original version of this article, unfortunately the article note was missed. The article note should be displayed as "Dr. Jean-Baptiste Pingault and Dr. Frühling Rijsdijk are shared senior authors". [Extracted from the article]

Objective: Recent studies have highlighted the impact of coexisting mental health problems in autism spectrum disorders (ASD). No twin studies to date have reported on individuals meeting diagnostic criteria of ASD. This twin study reports on the etiological overlap between the diagnosis of ASD and emotional symptoms, hyperactivity, and conduct problems measured with the Strengths and Difficulties Questionnaire.Method: Genetic and environmental influences on the covariance between ASD and coexisting problems were estimated, in line with the correlated risks model prediction. Phenotypic causality models were also fitted to explore alternative explanations of comorbidity: namely, that coexisting problems are the result of or result in ASD symptoms; that they increase recognition of ASD; or that they arise due to an over-observation bias/confusion when differentiating between phenotypes.Results: More than 50% of twins with broad spectrum/ASD met the borderline/abnormal levels cut-off criteria for emotional symptoms or hyperactivity, and approximately 25% met these criteria for the 3 reported problems. In comparison, between 13% and 16% of unaffected twins scored above the cut-offs. The phenotypic correlation between ASD and emotional symptoms was explained entirely by genetic influences and accompanied by a moderate genetic correlation (0.42). The opposite was true for the overlap with conduct problems, as nonshared-environmental factors had the strongest impact. For hyperactivity, the best-fitting model suggested a unidirectional phenotypic influence of hyperactivity on ASD.Conclusion: Our findings suggest a possible effect of hyperactivity on identification of ASD. The lack of genetic influences on conduct problems-ASD overlap further supports the genetic independence of these 2 phenotypes. Finally, the co-occurrence of emotional symptoms in ASD, compared to other co-occurring problems, is completely explained by common genetic effects. [ABSTRACT FROM AUTHOR]

Background: Positive, negative and disorganised psychotic symptom dimensions are associated with clinical and developmental variables, but differing definitions complicate interpretation. Additionally, some variables have had little investigation., Aims: To investigate associations of psychotic symptom dimensions with clinical and developmental variables, and familial aggregation of symptom dimensions, in multiple samples employing the same definitions., Method: We investigated associations between lifetime symptom dimensions and clinical and developmental variables in two twin and two general psychosis samples. Dimension symptom scores and most other variables were from the Operational Criteria Checklist. We used logistic regression in generalised linear mixed models for combined sample analysis ( n = 875 probands). We also investigated correlations of dimensions within monozygotic (MZ) twin pairs concordant for psychosis ( n = 96 pairs)., Results: Higher symptom scores on all three dimensions were associated with poor premorbid social adjustment, never marrying/cohabiting and earlier age at onset, and with a chronic course, most strongly for the negative dimension. The positive dimension was also associated with Black and minority ethnicity and lifetime cannabis use; the negative dimension with male gender; and the disorganised dimension with gradual onset, lower premorbid IQ and substantial within twin-pair correlation. In secondary analysis, disorganised symptoms in MZ twin probands were associated with lower premorbid IQ in their co-twins., Conclusions: These results confirm associations that dimensions share in common and strengthen the evidence for distinct associations of co-occurring positive symptoms with ethnic minority status, negative symptoms with male gender and disorganised symptoms with substantial familial influences, which may overlap with influences on premorbid IQ.

Existing evidence indicates genetic and non-genetic influences on sexual orientation; however, the possibility of gene-environment interplay has not been previously formally tested despite theories indicating this. Using a Finnish twin cohort, this study investigated whether childhood gender nonconformity and early-life adversities independently moderated individual differences in sexual orientation and childhood gender nonconformity, the relationship between them, and the etiological bases of the proposed moderation effects. Sexual orientation, childhood gender nonconformity, and early-life adversities were assessed using standard questionnaires. Structural equation twin model fitting was carried out using OpenMx. Childhood gender nonconformity was significantly associated with reduced phenotypic variance in sexual orientation (β =  - 0.14, 95% CI - 0.27, - 0.01). A breakdown of the underlying influences of this moderation effect showed that this was mostly due to moderation of individual-specific environmental influences which significantly decreased as childhood gender nonconformity increased (β E  =  - 0.38; 95% CI - 0.52, - 0.001) while additive genetic influences were not significantly moderated (β A  = 0.05; 95% CI - 0.30, 0.27). We also observed that the relationship between sexual orientation and childhood gender nonconformity was stronger at higher levels of childhood gender nonconformity (β = 0.10, 95% CI 0.05, 0.14); however, significance of the underlying genetic and environmental influences on this relationship could not be established in this sample. The findings indicate that beyond a correlation of their genetic and individual-specific environmental influences, childhood gender nonconformity is further significantly associated with reduced individual-specific influences on sexual orientation., (© 2023. The Author(s).)

Low- and middle-income countries (LMICs) globally have undergone rapid urbanisation, and changes in demography and health behaviours. In Sri Lanka, cardio-vascular disease and diabetes are now leading causes of mortality. High prevalence of their risk factors, including hypertension, dysglycaemia and obesity have also been observed. Diet is a key modifiable risk factor for both cardio-vascular disease and diabetes as well as their risk factors. Although typically thought of as an environmental risk factor, dietary choice has been shown to be genetically influenced, and genes associated with this behaviour correlate with metabolic risk indicators. We used Structural Equation Model fitting to investigate the aetiology of dietary choices and cardio-metabolic phenotypes in COTASS, a population-based twin and singleton sample in Colombo, Sri Lanka. Participants completed a Food Frequency Questionnaire (N = 3934) which assessed frequency of intake of 14 food groups including meat, vegetables and dessert or sweet snacks. Anthropometric (N = 3675) and cardio-metabolic (N = 3477) phenotypes were also collected including weight, blood pressure, cholesterol, fasting plasma glucose and triglycerides. Frequency of consumption of most food items was found to be largely environmental in origin with both the shared and non-shared environmental influences indicated. Modest genetic influences were observed for some food groups (e.g. fruits and leafy greens). Cardio-metabolic phenotypes showed moderate genetic influences with some shared environmental influence for Body Mass Index, blood pressure and triglycerides. Overall, it seemed that shared environmental effects were more important for both dietary choices and cardio-metabolic phenotypes compared to populations in the Global North., (© 2023. The Author(s).)

Nutrition and diet are key modifiable risk factors for the rising burden of non-communicable diseases like cardio-vascular diseases and diabetes in low- and middle- income countries (LMICs). The nutritional transition in dietary behaviours in LMICs has most likely contributed to this problem. Although traditionally assumed to be environmental, dietary choices are also genetically influenced. Twin study designs can be used to investigate the relative influence of genes and environment on nutrition intake, eating behaviours and associated psychological health. The overall aim of this project is to: provide proof-of-concept for the feasibility of using dietary (biomarker) data within the Children-of-Twin design in nutrition studies, develop laboratory skills and statistical genetic skills and establish a Sri Lankan-specific food composition database. Currently, a pilot study is being conducted with 304 individuals (38 Monozygotic twin pairs, 38 Dizygotic twin pairs and their male or female adult offspring). Questionnaire data on nutritional intake, eating behaviours, psychological well-being, physical health, and bio-specimens are being collected. A Sri Lankan-specific food composition database was developed, training sessions on macro and micro element analysis in biological samples and statistical genetics skills development were conducted and Community Engagement and Involvement programs were carried out in two districts of Sri Lanka., (© 2024. The Author(s).)

Following 602 Chinese twin pairs (48% male, all Han ethnicity) from primarily lower-than-average socioeconomic status families from early to mid-adolescence (M s  = 12 and 15 in 2006 and 2009), this study investigated gene-environment interplay between perceived parental supervision, peer drunkenness, and adolescent alcohol initiation. For alcohol initiation, shared environmental influences were initially negligible but became substantial. Genetic factors largely explained the links between both correlates with alcohol initiation. Parental supervision amplified genetic risks for alcohol initiation in early adolescence but suppressed it in mid-adolescence. Peer drunkenness augmented genetic and environmental influences at both times. Peer drunkenness showed stronger links and moderating potential than parental supervision. Chinese adolescents show dynamic gene-environment interplay patterns involving parent-child and peer processes in alcohol initiation., (© 2023 The Authors. Child Development © 2023 Society for Research in Child Development.)

Background: Insomnia with short sleep duration has been postulated as more severe than that accompanied by normal/long sleep length. While the short duration subtype is considered to have greater genetic influence than the other subtype, no studies have addressed this question. This study aimed to compare these subtypes in terms of: (1) the heritability of insomnia symptoms; (2) polygenic scores (PGS) for insomnia symptoms and sleep duration; (3) the associations between insomnia symptoms and a wide variety of traits/disorders., Methods: The sample comprised 4000 pairs of twins aged 16 from the Twins Early Development Study. Twin models were fitted to estimate the heritability of insomnia in both groups. PGS were calculated for self-reported insomnia and sleep duration and compared among participants with short and normal/long sleep duration., Results: Heritability was not significantly different in the short sleep duration group ( A  = 0.13 [95%CI = 0.01, 0.32]) and the normal/long sleep duration group ( A  = 0.35 [95%CI = 0.29, 0.40]). Shared environmental factors accounted for a substantial proportion of the variance in the short sleep duration group ( C  = 0.19 [95%CI = 0.05, 0.32]) but not in the normal/long sleep duration group ( C  = 0.00 [95%CI = 0.00, 0.04]). PGS did not differ significantly between groups although results were in the direction expected by the theory. Our results also showed that insomnia with short (as compared to normal/long) sleep duration had a stronger association with anxiety and depression ( p  < .05)-although not once adjusting for multiple testing., Conclusions: We found mixed results in relation to the expected differences between the insomnia subtypes in adolescents. Future research needs to further establish cut-offs for 'short' sleep at different developmental stages and employ objective measures of sleep., Competing Interests: Alice M. Gregory is an advisor for a project initially sponsored by Johnson's Baby. She is a consultant for Perrigo (2021+). She receives royalties for two books Nodding Off (Bloomsbury Sigma, 2018) and The Sleepy Pebble (Flying Eye, 2019). She has another contract with Lawrence King Publishers (publication due 2023). She was previously a CEO of Sleep Universal LTD (2022). She is a regular contributor to BBC Focus magazine and has contributed to other outlets (such as The Conversation, The Guardian and Balance Magazine). She occasionally receives sample products related to sleep (e.g., blue light blocking glasses) and has given a paid talk to a business (Investec). She is a specialist subject editor at JCPP (sleep) for which she receives a small honorarium. She has contributed a paid article to Neurodiem. The remaining authors have declared they have no competing or potential conflicts of interest., (© 2023 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Objective: Evidence about the etiology of the predictive associations between a diagnosis of ADHD and cognitive performance over time is scarce. Here, we examine these predictive and etiological patterns using a cross-lagged model design in a sample of 404 participants (74% males) from ADHD and control sibling pairs aged 6 to 17 years at baseline and 12 to 24 years at follow-up., Methods: Data included IQ, short-term and working memory measures, and response speed and variability from a four-choice reaction-time task., Results: ADHD and IQ predicted each other over time. ADHD at baseline predicted lower working memory performance at follow-up. Stable etiological influences emerged in the association between ADHD and cognitive variables across time., Conclusion: Whether early interventions can reduce negative interference with learning at school requires further study.

Although health disparities among same-sex attracted compared to heterosexual individuals are typically explained by minority stress, there is limited evidence for a causal effect. This study investigated whether same-sex attraction was causally associated with psychological distress and risky sexual behavior using sociosexual behavior as a proxy. The sample comprised monozygotic and dizygotic twins and their non-twin siblings (n = 2036, 3780 and 2356, respectively) genotyped and assessed for same-sex attraction, psychological distress (anxiety and depressive symptoms), and risky sexual behavior. Causal influences were investigated with same-sex attraction as the predictor and psychological distress and risky sexual behavior as the outcomes in two separate Mendelian Randomization-Direction of Causation (MRDoC) models using OpenMx in R. The MRDoC model improves on the Mendelian Randomization and Direction of Causation twin models by allowing analyses of variables with similar genetic architectures, incorporating polygenic scores as instrumental variables and specifying pleiotropy and residual covariance. There were significant causal influences flowing from same-sex attraction to psychological distress and risky sexual behavior (standardized coefficients = 0.13 and 0.16; 95% CIs 0.03-0.23 and 0.08-0.25, respectively). Further analyses also demonstrated causal influences flowing from psychological distress and risky sexual behavior toward same-sex attraction. Causal influences from same-sex attraction to psychological distress and risky sexual behavior may reflect minority stress, which reinforces ongoing measures to minimize social disparities. Causal influences flowing in the opposite direction may reflect rejection sensitivity, stigma-inducing outcomes of risky sexual behavior, and recall bias; however, further research is required to specifically investigate these processes., (© 2022. The Author(s).)

Only one study has examined bidirectional causality between sexual minority status (having same-sex attraction) and psychological distress. We combined twin and genomic data from 8700 to 9700 participants in the UK Twins Early Development Study cohort at ≈21 years to replicate and extend these bidirectional causal effects using separate unidirectional Mendelian Randomization-Direction of Causation models. We further modified these models to separately investigate sex differences, moderation by childhood factors (retrospectively-assessed early-life adversity and prospectively-assessed childhood gender nonconformity), and mediation by victimization. All analyses were carried out in OpenMx in R. Same-sex attraction causally influenced psychological distress with significant reverse causation (beta = 0.19 and 0.17; 95% CIs = 0.09, 0.29 and 0.08, 0.25 respectively) and no significant sex differences. The same-sex attraction → psychological distress causal path was partly mediated by victimization (12.5%) while the reverse causal path was attenuated by higher childhood gender nonconformity (moderation coefficient = -0.09, 95% CI: -0.13, -0.04)., (© 2022. The Author(s).)

Previous genetically informed studies have uncovered likely causal relationships between mental health problems and self-harm but resulting causal estimates may be biased due to unmediated pleiotropy. By fitting Mendelian Randomization - Direction of Causation (MR-DoC) models that explicitly model pleiotropy, we investigated the effect of four quantitatively measured mental health problems - major depressive disorder (MDD), schizophrenia, attention-deficit hyperactivity disorder (ADHD), and insomnia, on non-suicidal self-harm (NSSH) and suicidal self-harm (SSH), separately. We used data of 12,723 twins (56.6% females) in the Twins Early Development Study. Besides substantial pleiotropy, we found effects from child-rated depressive symptoms to both NSSH (β = 0.194, 95% CIs: 0.131, 0.257) and SSH (β = 0.210, 95% CIs: 0.125, 0.295). Similarly, effects flowed from parent-rated depressive symptoms to NSSH (β = 0.092, 95% CIs: 0.004, 0.181) and SSH (β = 0.165, 95% CIs: 0.051, 0.281). We did not find evidence of aetiological difference between NSSH and SSH., (© 2022. The Author(s).)

Background: Genetic influences are ubiquitous as virtually all phenotypes and most exposures typically classified as environmental have been found to be heritable. A polygenic score summarises the associations between millions of genetic variants and an outcome in a single value for each individual. Ever lowering costs have enabled the genotyping of many samples relevant to child psychology and psychiatry research, including cohort studies, leading to the proliferation of polygenic score studies. It is tempting to assume that associations detected between polygenic scores and phenotypes in those studies only reflect genetic effects. However, such associations can reflect many pathways (e.g. via environmental mediation) and biases., Methods: Here, we provide a comprehensive overview of the many reasons why associations between polygenic scores, environmental exposures, and phenotypes exist. We include formal representations of common analyses in polygenic score studies using structural equation modelling. We derive biases, provide illustrative empirical examples and, when possible, mention steps that can be taken to alleviate those biases., Results: Structural equation models and derivations show the many complexities arising from jointly modelling polygenic scores with environmental exposures and phenotypes. Counter-intuitive examples include that: (a) associations between polygenic scores and phenotypes may exist even in the absence of direct genetic effects; (b) associations between child polygenic scores and environmental exposures can exist in the absence of evocative/active gene-environment correlations; and (c) adjusting an exposure-outcome association for a polygenic score can increase rather than decrease bias., Conclusions: Strikingly, using polygenic scores may, in some cases, lead to more bias than not using them. Appropriately conducting and interpreting polygenic score studies thus requires researchers in child psychology and psychiatry and beyond to be versed in both epidemiological and genetic methods or build on interdisciplinary collaborations., (© 2022 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Young adulthood is a key developmental period for understanding outcomes of childhood onset attention-deficit/hyperactivity disorder (ADHD) and autism. Measurement of functional impairment and quality of life (QoL) can provide important information on the real-life challenges associated with these conditions. Event-related potential (ERP) measures from the continuous performance task (CPT) have long been identified as altered in ADHD and autism but the role of these functions in the aetiological pathway to the disorders and associated impact on quality of life in young adulthood is unknown., Method: We investigated the relationships between ADHD and autism, functional impairment, quality of life, and ERP measures from the cued CPT (CPT-OX) in a young adult twin sample (566 participants aged 22.43 ± 0.96 years old)., Results: We observed significant phenotypic correlations between ADHD/autism and lower quality of life with specific genetic overlap between ADHD and physical health, psychological, and environmental aspects. We found significant phenotypic and genetic correlations between ADHD and functional impairment in all domains, as well as between autism and impairment in social functioning and lower impairment in risk-taking. Both ADHD and autism were associated with attenuated amplitude of inhibitory and proactive control ERPs, with large genetic contributions to the overlap. We also found significant phenotypic correlations between these ERP measures and Weiss Functional Impairment Rating Scale (WFIRS) and QoL., Conclusion: This is the first study to investigate the phenotypic and genetic relationships between ADHD and autism, functional impairment, quality of life and ERP measures in young adulthood. Our findings could represent a step towards identifying ERP measures that are related to behaviour in the absence of overt symptoms., Competing Interests: The authors have declared that they have no competing or potential conflicts of interest., (© 2022 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Previous research indicates that body dysmorphic disorder (BDD) is associated with risk of suicidality. However, studies have relied on small and/or specialist samples and largely focussed on adults, despite these difficulties commonly emerging in youth. Furthermore, the aetiology of the relationship remains unknown., Methods: Two independent twin samples were identified through the Child and Adolescent Twin Study in Sweden, at ages 18 (N = 6027) and 24 (N = 3454). Participants completed a self-report measure of BDD symptom severity. Young people and parents completed items assessing suicidal ideation/behaviours. Logistic regression models tested the association of suicidality outcomes with: (a) probable BDD, classified using an empirically derived cut-off; and (b) continuous scores of BDD symptoms. Bivariate genetic models examined the aetiology of the association between BDD symptoms and suicidality at both ages., Results: Suicidal ideation and behaviours were common among those with probable BDD at both ages. BDD symptoms, measured continuously, were linked with all aspects of suicidality, and associations generally remained significant after adjusting for depressive and anxiety symptoms. Genetic factors accounted for most of the covariance between BDD symptoms and suicidality (72.9 and 77.7% at ages 18 and 24, respectively), but with significant non-shared environmental influences (27.1 and 22.3% at ages 18 and 24, respectively)., Conclusions: BDD symptoms are associated with a substantial risk of suicidal ideation and behaviours in late adolescence and early adulthood. This relationship is largely explained by common genetic liability, but non-shared environmental effects are also significant and could provide opportunities for prevention among those at high-risk.

Objective: Depression often co-occurs with poor health-related quality of life (HRQL). Twin studies report genetic and individual-level environmental underpinnings in the aetiology of both depression and HRQL, but there is limited twin research exploring this association further. There is also little evidence on sex differences and non-Western populations are underrepresented. In this paper we explored the phenotypic and aetiological relationship between depressive symptoms and HRQL and possible sex differences in a low-middle-income Sri Lankan population., Method: Data for 3,948 participants came from the Colombo Twin and Singleton Follow-up Study (CoTaSS-2). Using self-report measures of depressive symptoms and HRQL, we conducted univariate and bivariate sex-limitation twin analyses., Results: Depressive symptoms showed moderate genetic (33%) and strong nonshared environmental influences (67%). Nonshared environment accounted for the majority of variance in all the subscales of HRQL (ranging from 68 to 93%), alongside small genetic influences (ranging from 0 to 23%) and shared environmental influences (ranging from 0 to 28%). Genetic influences were significant for emotional wellbeing (23%). Shared environmental influences were significant for four out of the eight HRQL variables (ranging from 22-28%), and they were more prominent in females than males. Depressive symptoms were significantly associated with lower HRQL scores. These correlations were mostly explained by overlapping nonshared environmental effects. For traits related to emotional functioning, we also detected substantial overlapping genetic influences with depressive symptoms., Conclusions: Our study confirmed previous findings of a negative association between depressive symptoms and HRQL. However, some of the aetiological factors of HRQL differed from Western studies, particularly regarding the effects of shared environment. Our findings highlight the importance of cross-cultural research in understanding associations between psychological wellbeing and HRQL., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Risky sexual behavior among sexual minorities (lesbian, gay, and bisexual individuals) are partly attributed to mental health and other social disparities; but this may be confounded by correlated genetic and environmental influences. As preregistered, the present study investigated indirect associations between sexual minority status and increased lifetime sexual partners through increased psychosocial adversity (depressive and anxiety symptoms, intimate partner violence, and early life adversities) and substance use (alcohol, cannabis, and other illicit drugs), confounding by correlated genetic and environmental influences, and sex differences in these relationships., Method: The sample comprised sexual minority and heterosexual twins who participated in the first and second phases of the latest wave of data collection in the U.K. population-based Twins Early Development study cohort (June 2017 through February 2019; n = 9,697 and 8,718, respectively, M age = 22.3 ± .92 years). Structural equation modeling was used to specify psychosocial adversity and substance use as mediators while genetic and environmental confounding was further determined by biometrical genetic analyses in which similarities in identical and nonidentical twins were compared., Results: Increased psychosocial adversity and substance use fully mediated increased lifetime sexual partners in sexual minority women while this effect was partial (31.1%) in men. The best-fitting genetic models indicated that these relationships were not confounded by correlated genetic and environmental influences., Conclusions: The relationships between sexual minority status, psychosocial adversity, substance use, and sexual health disparities appeared independent of genetic and environmental influences. Individual and systemic interventions to reduce psychosocial disadvantage and substance use can also decrease sexual health disparities among sexual minorities. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Obsessive-compulsive disorder (OCD) has been linked with elevated risk of suicidality. However, most previous studies have been cross-sectional, and little is known about the aetiology of the association between obsessive-compulsive symptoms (OCS) and suicidality in young adults., Methods: Participants were members of the Child and Adolescent Twin Study in Sweden, at ages 18 (n = 9,162) and 24 (n = 3,466). Twins completed self-report measures, including assessment of OCS, suicidal ideation, and suicidal attempts. Logistic regression models tested concurrent and prospective associations of total OCS and OCS dimensions with suicidality, with and without adjustment for depression and anxiety symptoms. Genetic models tested the extent to which the main phenotypic associations were accounted for by genetic and environmental influences., Results: Total OCS were significantly associated with concurrent reports of suicidality at age 18 and 24, even when controlling for depressive and anxiety symptoms. Taboo obsessions (e.g., sexual and aggressive thoughts) were more robustly associated with suicidality than other OCS dimensions, and prospectively predicted suicidality symptoms over time, even when controlling for baseline suicide attempts. Genetic factors accounted for most of the concurrent and longitudinal covariance between OCS and suicidality, with substantial non-shared environmental influences., Limitations: We relied on self-report measures and did not include diagnostic assessment of OCD., Conclusions: OCS, particularly taboo obsessions, are associated with significantly elevated risk of suicidality in late adolescence and early adulthood. This relationship is explained by a combination of common genetic liability and non-shared environmental effects, suggesting that effective OCS treatment might reduce suicidality risk in this group., (Copyright © 2020. Published by Elsevier B.V.)

Objective: Previous studies in children with ADHD identified two partially separable familial factors underlying cognitive dysfunction, but evidence in adolescents and adults is lacking. Here, we investigate the etiological structure of cognitive-neurophysiological impairments in ADHD in adolescents and young adults. Method: Factor analyses and multivariate familial models were run in 356 participants from ADHD and control sibling pairs aged 11 to 27 years on data on IQ, digit span forward (DSF) and backward (DSB), and cognitive-performance and event-related potential (ERP) measures from three cognitive tasks. Results: Three familial factors (cF 1-3 ), showing substantial familial overlap with ADHD, captured the familial covariation of ADHD with nine cognitive-ERP measures. cF 1 loaded on IQ, mean reaction time (MRT), and reaction-time variability (RTV); cF 2 on DSF and DSB; and cF 3 on number of errors and ERPs of inhibition and error processing. Conclusion: These results identify three partially separable etiological pathways leading to cognitive-neurophysiological impairments in adolescent and adult ADHD.

Background: Studies have reported that impulsivity predicts childhood BMI and that the association is mediated by eating behaviors. One aspect of impulsivity-potentially crucial in the obesity context-is reward responsiveness, which may predispose to responsiveness to palatable food cues. The behavioral susceptibility theory hypothesizes that genetic susceptibility to obesity operates partly via genetically determined differences in appetite regulation. Reward responsiveness may therefore be one of the neuro-endophenotypes that mediates genetic susceptibility to obesity., Objective: To test whether reward responsiveness, eating behaviors, and child BMI share common genetic architecture., Methods: We examined reward responsiveness, eating behaviors, and BMI in 5-year-old children from Gemini, a UK birth cohort of 2402 twin pairs born in 2007. All measures were collected by parent report. Reward responsiveness was derived from the Behavioral Approach System. Compulsion to eat and eating for pleasure was measured with the "food responsiveness" scale of the Child Eating Behavior Questionnaire. Wanting to eat in response to environmental food cues was measured with the "external eating" scale of the Dutch Eating Behavior Questionnaire. Maximum-likelihood structural equation modeling was used to establish underlying common genetic and environmental influences., Results: There were significant positive phenotypic correlations between all traits except for reward responsiveness and BMI. Genetic factors explained the majority of the association between food responsiveness and external eating (74%, 95% CI: 61, 87), whereas common shared environmental factors explained the majority of the associations between reward responsiveness with both food responsiveness (55%, 95% CI: 20, 90) and external eating (70%, 95% CI: 39, 100)., Conclusions: Our study demonstrates the importance of common environmental factors in the shared etiology between reward responsiveness and childhood eating behaviors. However, the common etiology underlying both reward responsiveness and BMI is unclear, as there was no phenotypic correlation between reward responsiveness and BMI at this age. Further longitudinal research needs to detangle this complex relationship throughout development.

Increased risky sexual behavior in sexual minorities relative to heterosexual individuals may be partly explained by mental health disparities, and both factors may be further jointly influenced by common genetic and environmental factors. However, these relationships have not been previously investigated. The objectives of the present study were to investigate mental health disparities as a mediator of the relationship between sexual orientation and risky sexual behavior, controlling for genetic and environmental effects in this relationship and testing for sex differences. Participants included 5814 twins from a Finnish twin cohort. Specified latent factors included sexual orientation, mental health indicators, and risky sexual behavior. Twin models were fitted to the factor structure of the data whereby a Cholesky decomposition on the factors was compared to a mediation submodel using OpenMx. Sex differences were tested in the final model. Phenotypically, mental health disparities partially mediated the relationship between sexual orientation and increased risky sexual behavior, with comparable effects in males and females. However, while this indirect route from sexual orientation to risky sexual behavior mainly contained transmitted genetic effects in males, there was a significant proportion of transmitted shared environmental effects in females. This is the first study to demonstrate that the mediation relationships between sexual orientation, mental health disparities, and risky sexual behavior are not confounded by genetic and environmental factors. The significant sex differences need to be recognized in future research and intervention design to improve sexual health in sexual minorities.

Background: Identifying causal risk factors for self-harm is essential to inform preventive interventions. Epidemiological studies have identified risk factors associated with self-harm, but these associations can be subject to confounding. By implementing genetically informed methods to better account for confounding, this study aimed to better identify plausible causal risk factors for self-harm., Methods and Findings: Using summary statistics from 24 genome-wide association studies (GWASs) comprising 16,067 to 322,154 individuals, polygenic scores (PSs) were generated to index 24 possible individual risk factors for self-harm (i.e., mental health vulnerabilities, substance use, cognitive traits, personality traits, and physical traits) among a subset of UK Biobank participants (N = 125,925, 56.2% female) who completed an online mental health questionnaire in the period from 13 July 2016 to 27 July 2017. In total, 5,520 (4.4%) of these participants reported having self-harmed in their lifetime. In binomial regression models, PSs indexing 6 risk factors (major depressive disorder [MDD], attention deficit/hyperactivity disorder [ADHD], bipolar disorder, schizophrenia, alcohol dependence disorder, and lifetime cannabis use) predicted self-harm, with effect sizes ranging from odds ratio (OR) = 1.05 (95% CI 1.02 to 1.07, q = 0.008) for lifetime cannabis use to OR = 1.20 (95% CI 1.16 to 1.23, q = 1.33 × 10-35) for MDD. No systematic differences emerged between suicidal and non-suicidal self-harm. To further probe causal relationships, two-sample Mendelian randomisation (MR) analyses were conducted, with MDD, ADHD, and schizophrenia emerging as the most plausible causal risk factors for self-harm. The genetic liabilities for MDD and schizophrenia were associated with self-harm independently of diagnosis and medication. Main limitations include the lack of representativeness of the UK Biobank sample, that self-harm was self-reported, and the limited power of some of the included GWASs, potentially leading to possible type II error., Conclusions: In addition to confirming the role of MDD, we demonstrate that ADHD and schizophrenia likely play a role in the aetiology of self-harm using multivariate genetic designs for causal inference. Among the many individual risk factors we simultaneously considered, our findings suggest that systematic detection and treatment of core psychiatric symptoms, including psychotic and impulsivity symptoms, may be beneficial among people at risk for self-harm., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: CML sits on the R&D Scientific Advisory Board for Myriad Neuroscience; CML is a member of the Editorial Board of PLOS Medicine.

Objective: Results from twin studies examining the genetic overlap between type 2 diabetes and depression are currently inconclusive. This question has not been addressed in non-Western populations. We aimed to examine whether there are common genetic factors between type 2 diabetes and depression in a Sri Lankan population using genetic model-fitting analysis., Method: The Colombo Twin and Singleton Study-Phase 2 consists of 2019 singletons, and 842 monozygotic and 578 dizygotic twin pairs. The primary outcomes were self-reported type 2 diabetes diagnosis and Beck Depression Inventory scores. Standard bivariate twin models were fitted to estimate the genetic and environmental (co)variance of type 2 diabetes and depression., Results: In the best-fitting model, the phenotypic correlation between type 2 diabetes and depression was significant in female individuals only (r = 0.15 [0.08-0.21]). This association was primarily attributed to a significant genetic correlation between the traits (rA = 0.53 [0.19-0.98])., Conclusions: In female individuals, but not male individuals, we found a significant genetic overlap between type 2 diabetes and depression in the context of a modest phenotypic correlation.

Causal inference is essential across the biomedical, behavioural and social sciences.By progressing from confounded statistical associations to evidence of causal relationships, causal inference can reveal complex pathways underlying traits and diseases and help to prioritize targets for intervention. Recent progress in genetic epidemiology - including statistical innovation, massive genotyped data sets and novel computational tools for deep data mining - has fostered the intense development of methods exploiting genetic data and relatedness to strengthen causal inference in observational research. In this Review, we describe how such genetically informed methods differ in their rationale, applicability and inherent limitations and outline how they should be integrated in the future to offer a rich causal inference toolbox.

Common genetic influences offer a partial explanation for comorbidity between different psychiatric disorders 1-3 . However, the genetics underlying co-development-the cross-domain co-occurrence of patterns of change over time-of psychiatric symptoms during childhood and adolescence has not been well explored. Here, we show genetic influence on joint symptom trajectories of parent-reported conduct and emotional problems (overall N = 15,082) across development (4-16 years) using both twin- and genome-wide polygenic score analyses (genotyped N = 2,610). Specifically, we found seven joint symptom trajectories, including two characterized by jointly stable and jointly increasing symptoms of conduct and emotional problems, respectively (7.3% of the sample, collectively). Twin modelling analyses revealed substantial genetic influence on trajectories (heritability estimates range of 0.41-0.78). Furthermore, individuals' risk of being classified in the most symptomatic trajectory classes was significantly predicted by polygenic scores for years-of-education-associated alleles and depressive symptoms-associated alleles. Complementary analyses of child self-reported symptoms across late childhood and early adolescence yielded broadly similar results. Taken together, our results indicate that genetic factors are involved in the co-development of conduct and emotional problems across childhood and adolescence, and that individuals with co-developing symptoms across multiple domains may represent a clinical subgroup characterized by increased levels of genetic risk.

Emotional overeating (EOE) is the tendency to eat more in response to negative emotions; its etiology in early life is unknown. We established the relative genetic and environmental influences on EOE in toddlerhood and early childhood. Data were from Gemini, a population-based cohort of 2,402 British twins born in 2007. EOE was measured using the "emotional overeating" scale of the Child Eating Behavior Questionnaire (CEBQ) at 16 months and 5 years. A longitudinal quantitative genetic model established that genetic influences on EOE were minimal; on the other hand, shared environmental influences explained most of the variance. EOE was moderately stable from 16 months to 5 years and continuing environmental factors shared by twin pairs at both ages explained the longitudinal association., (© 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.)

Aims/hypothesis: The discordance status of (autoimmune) type 1 diabetes within monozygotic twin pairs points to the importance of environmental factors. The aim of this study was to investigate whether the environmental events causing type 1 diabetes influence thyroid autoimmunity., Methods: Monozygotic and dizygotic twins discordant for type 1 diabetes from the UK and USA were tested for thyroid peroxidase autoantibodies (TPOA) by radioimmunoassay. Using quantitative genetic model fitting of a liability-threshold model we estimated the contribution of genetic (heritability) and environmental factors to TPOA., Results: TPOA positivity was higher in females than in males in both cohorts and was associated with later age at diagnosis in the UK and combined cohorts (p < 0.01). TPOA did not specifically segregate with type 1 diabetes in the twin pairs (p > 0.2 in all groups). The best-fitting models showed heritability (95% CI) estimates for TPOA of 63% (37%, 80%) for the UK and 80% (51%, 92%) for US twins, while the best-fitting meta-analysis model of the two twin cohorts combined included additive genetic and unique environmental factors with a heritability estimate of 69% (50%, 82%)., Conclusions/interpretation: Risk of thyroid autoimmunity, defined by TPOA, in the context of autoimmune diabetes is, substantially, genetically determined in discordant twin pairs. Environmental factors leading to type 1 diabetes were not the same as those involved with thyroid autoimmunity. It follows that it is as important to investigate for thyroid autoimmunity in relatives of type 1 diabetes patients as it is in the patients themselves.

The Twin Interdisciplinary Neuroticism Study (TWINS) is a three-wave study including >800 twin pairs from the northern part of the Netherlands. The aim of the study is to unravel why neuroticism reflects vulnerability to mental disorders. In this study, we focus on possible mechanisms underlying this vulnerability and their genetic and environmental origins. In total, 125 female twin pairs visited our psychophysiological laboratory. From these twin pairs DNA was isolated and both candidate gene and genome-wide genotyping were conducted. Future work includes studies of candidate genes. The study also participates in several meta-genome-wide association study (GWAS) consortia.

Background: Somatic symptoms often co-occur with psychological symptoms but this overlap is poorly understood. Some aspects of this overlap differ in the South Asian context, but it is not clear whether this is a reporting effect or an underlying difference in experienced illness., Methods: Home interviews were administered to 4,024 twins randomly selected from a population-based twin register in the Colombo district of Sri Lanka (the CoTASS study). These included assessments of psychological, somatic and fatigue symptoms. The data were analyzed using factor analytic and quantitative genetic approaches., Results: Confirmatory factor analysis showed that the symptoms from the three scales represented three separate dimensions, rather than all tapping into a single dimension. However, familial correlations among the data were most consistent with a common pathway model. This implies that a portion of the underlying vulnerability is common across psychological, fatigue and somatic symptoms. There were sex differences in the etiology of this model, with shared environmental and genetic influences playing different roles in men and women., Conclusions: There is a complex etiological relationship between psychological, fatigue and somatic symptoms. This is similar in Sri Lanka to Western countries, but there may be a greater influence from the family environment, suggesting that care needs to be taken when generalizing research findings between countries. People who complain of certain fatigue or somatic symptoms may well also have psychological symptoms, or may have genetic or environmental vulnerabilities to such problems.

Background: There is a substantial overlap between genes affecting anxiety and depression. Both anxiety and depression are associated with cognitive biases such as anxiety sensitivity and attributional style. Little, however, is known about the relationship between these variables and whether these too are genetically correlated., Methods: Self-reports of anxiety sensitivity, anxiety symptoms, attributional style and depression symptoms were obtained for over 1300 adolescent twin and sibling pairs at two time points. The magnitude of genetic and environmental influences on the measures was examined., Results: Strongest associations were found between anxiety sensitivity and anxiety ratings at both measurement times (r=.70, .72) and between anxiety and depression (r=.62 at both time points). Correlations between the cognitive biases were modest at time 1 (r=-.12) and slightly larger at time 2 (r=-.31). All measures showed moderate genetic influence. Generally genetic correlations reflected phenotypic correlations. Thus the highest genetic correlations were between anxiety sensitivity and anxiety ratings (.86, .87) and between anxiety and depression ratings (.77, .71). Interestingly, depression ratings also showed a high genetic correlation with anxiety sensitivity (.70, .76). Genetic correlations between the cognitive bias measures were moderate (-.31, -.46)., Limitations: The sample consists primarily of twins, there are limitations associated with the twin design., Conclusions: Cognitive biases associated with depression and anxiety are not as genetically correlated as anxiety and depression ratings themselves. Further research into the cognitive processes related to anxiety and depression will facilitate understanding of the relationship between bias and symptoms.

Objective: To investigate the longitudinal development of callous-unemotional traits (CU) in middle childhood using developmental trajectory analyses in a large twin dataset and examine the degree to which genetic and environmental influences contributed to the CU trajectory-group membership in children., Method: The study included 9,462 youths from the Twins Early Development Study, a population-based sample of twins from the United Kingdom. Developmental trajectories were described using teachers' ratings of CU at 7, 9, and 12 years old., Results: We identified four trajectories of CU through general growth mixture modeling: stable high, increasing, decreasing, and stable low. In most cases, the trajectory-group membership was largely driven by genetic and to a lesser extent by nonshared environmental influences for boys and girls. The most notable exception was a strong contribution of shared environment for the girls in the stable-high trajectory group., Conclusions: Our findings suggest distinct developmental trajectories of CU from childhood to early adolescence, which are in most cases influenced by genetic factors and, to a lesser degree, by nonshared environmental factors. Highest heritability was observed for boys on a stable-high CU trajectory. Interestingly, the trajectory-group membership for girls on a stable-high CU trajectory appeared to be almost entirely driven by shared environmental influences. These differences in the etiology of stable-high CU in boys and girls have potential implications for clinical practice and studies attempting to identify genetic and environmental risk factors for high CU., (2010 American Academy of Child and Adolescent Psychiatry. All rights reserved.)

Background: Previous reports of genetic influences on obsessive-compulsive disorder (OCD) symptoms have suggested moderate heritability. Family history studies of co-morbidity have found familial aggregation with tics, especially for early-onset OCD, and familial aggregation with anxiety disorders., Method: Heritability of OCD and familial aggregation of OCD, tics and anxiety disorders were investigated in a community sample of 6-year-old twins using a two-phase design in which 4662 twin pairs were sampled and 854 pairs were assessed in the second phase by maternal-informant diagnostic interview using DSM-IV criteria., Results: In the multivariate model combined additive genetic and common environmental effects were estimated as 47% for sub-threshold OCD, and the model was unable to distinguish these sources of familial aggregation. There were strong familial aggregations between sub-threshold OCD and tics and between sub-threshold OCD and other anxiety disorders (80% and 97% respectively), although again specific sources could not be distinguished., Conclusions: The findings are consistent with the hypothesis of a tic-related early-onset OCD phenotype, but also with the hypothesis of an anxiety-related early-onset OCD phenotype.

The classical twin study is the most popular design in behavioural genetics. It has strong roots in biometrical genetic theory, which allows predictions to be made about the correlations between observed traits of identical and fraternal twins in terms of underlying genetic and environmental components. One can infer the relative importance of these 'latent' factors (model parameters) by structural equation modelling (SEM) of observed covariances of both twin types. SEM programs estimate model parameters by minimising a goodness-of-fit function between observed and predicted covariance matrices, usually by the maximum-likelihood criterion. Likelihood ratio statistics also allow the comparison of fit of different competing models. The program Mx, specifically developed to model genetically sensitive data, is now widely used in twin analyses. The flexibility of Mx allows the modelling of multivariate data to examine the genetic and environmental relations between two or more phenotypes and the modelling to categorical traits under liability-threshold models.