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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.
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Diabetes Mellitus , Enfermedades Vasculares , Humanos , Sri Lanka/epidemiología , Obesidad/genética , Factores de Riesgo , TriglicéridosRESUMEN
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.
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Gemelos Dicigóticos , Gemelos Monocigóticos , Adulto , Femenino , Humanos , Masculino , Enfermedades en Gemelos/genética , Estudios de Factibilidad , Proyectos Piloto , Gemelos Dicigóticos/genética , Gemelos Monocigóticos/genética , Hijos AdultosRESUMEN
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.
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Minería de Datos/métodos , Bases de Datos Genéticas , Genotipo , Técnicas de Genotipaje , HumanosRESUMEN
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 (ß = - 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 (ßE = - 0.38; 95% CI - 0.52, - 0.001) while additive genetic influences were not significantly moderated (ßA = 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 (ß = 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.
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Interacción Gen-Ambiente , Conducta Sexual , Humanos , Masculino , Femenino , Finlandia , Adulto , Conducta Sexual/psicología , Experiencias Adversas de la Infancia , Minorías Sexuales y de Género/psicología , Encuestas y Cuestionarios , Persona de Mediana Edad , Identidad de Género , NiñoRESUMEN
Associations between exposures and outcomes reported in epidemiological studies are typically unadjusted for genetic confounding. We propose a two-stage approach for estimating the degree to which such observed associations can be explained by genetic confounding. First, we assess attenuation of exposure effects in regressions controlling for increasingly powerful polygenic scores. Second, we use structural equation models to estimate genetic confounding using heritability estimates derived from both SNP-based and twin-based studies. We examine associations between maternal education and three developmental outcomes - child educational achievement, Body Mass Index, and Attention Deficit Hyperactivity Disorder. Polygenic scores explain between 14.3% and 23.0% of the original associations, while analyses under SNP- and twin-based heritability scenarios indicate that observed associations could be almost entirely explained by genetic confounding. Thus, caution is needed when interpreting associations from non-genetically informed epidemiology studies. Our approach, akin to a genetically informed sensitivity analysis can be applied widely.
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Factores de Confusión Epidemiológicos , Adulto , Trastorno por Déficit de Atención con Hiperactividad/genética , Índice de Masa Corporal , Niño , Desarrollo Infantil , Escolaridad , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
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 â 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).
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Distrés Psicológico , Minorías Sexuales y de Género , Humanos , Masculino , Femenino , Niño , Estudios Retrospectivos , Identidad de Género , CausalidadRESUMEN
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.
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Distrés Psicológico , Conducta Sexual , Humanos , Conducta Sexual/psicología , Gemelos , Heterosexualidad , Ansiedad/psicologíaRESUMEN
Following 602 Chinese twin pairs (48% male, all Han ethnicity) from primarily lower-than-average socioeconomic status families from early to mid-adolescence (Ms = 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.
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Conducta del Adolescente , Consumo de Bebidas Alcohólicas , Intoxicación Alcohólica , Adolescente , Femenino , Humanos , Masculino , Intoxicación Alcohólica/genética , Pueblos del Este de Asia , Padres , Grupo Paritario , Responsabilidad Parental , Interacción Gen-Ambiente , NiñoRESUMEN
BACKGROUND: While studies from the start of the COVID-19 pandemic have described initial negative effects on mental health and exacerbating mental health inequalities, longer-term studies are only now emerging. METHOD: In total, 34 465 individuals in the UK completed online questionnaires and were re-contacted over the first 12 months of the pandemic. We used growth mixture modelling to identify trajectories of depression, anxiety and anhedonia symptoms using the 12-month data. We identified sociodemographic predictors of trajectory class membership using multinomial regression models. RESULTS: Most participants had consistently low symptoms of depression or anxiety over the year of assessments (60%, 69% respectively), and a minority had consistently high symptoms (10%, 15%). We also identified participants who appeared to show improvements in symptoms as the pandemic progressed, and others who showed the opposite pattern, marked symptom worsening, until the second national lockdown. Unexpectedly, most participants showed stable low positive affect, indicating anhedonia, throughout the 12-month period. From regression analyses, younger age, reporting a previous mental health diagnosis, non-binary, or self-defined gender, and an unemployed or a student status were significantly associated with membership of the stable high symptom groups for depression and anxiety. CONCLUSIONS: While most participants showed little change in their depression and anxiety symptoms across the first year of the pandemic, we highlight the divergent responses of subgroups of participants, who fared both better and worse around national lockdowns. We confirm that previously identified predictors of negative outcomes in the first months of the pandemic also predict negative outcomes over a 12-month period.
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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.
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Trastorno Dismórfico Corporal , Suicidio , Adolescente , Trastorno Dismórfico Corporal/epidemiología , Trastorno Dismórfico Corporal/genética , Niño , Humanos , Factores de Riesgo , Autoinforme , Ideación Suicida , Suecia/epidemiología , Adulto JovenRESUMEN
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 (ß = 0.194, 95% CIs: 0.131, 0.257) and SSH (ß = 0.210, 95% CIs: 0.125, 0.295). Similarly, effects flowed from parent-rated depressive symptoms to NSSH (ß = 0.092, 95% CIs: 0.004, 0.181) and SSH (ß = 0.165, 95% CIs: 0.051, 0.281). We did not find evidence of aetiological difference between NSSH and SSH.
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Trastorno Depresivo Mayor , Conducta Autodestructiva , Femenino , Humanos , Masculino , Trastorno Depresivo Mayor/genética , Conducta Autodestructiva/genética , Factores de Riesgo , Causalidad , Ideación Suicida , Estudio de Asociación del Genoma CompletoRESUMEN
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.
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Midazolam , Herencia Multifactorial , Estudios de Cohortes , Exposición a Riesgos Ambientales/efectos adversos , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , FenotipoRESUMEN
BACKGROUND: Parental criticism is correlated with internalising symptoms in adolescent offspring. This correlation could in part reflect their genetic relatedness, if the same genes influence behaviours in both parents and offspring. We use a Children-of-Twins design to assess whether parent-reported criticism and offspring internalising symptoms remain associated after controlling for shared genes. To aid interpretation of our results and those of previous Children-of-Twins studies, we examine statistical power for the detection of genetic effects and explore the direction of possible causal effects between generations. METHODS: Data were drawn from two Swedish twin samples, comprising 876 adult twin pairs with adolescent offspring and 1,030 adolescent twin pairs with parents. Parent reports of criticism towards their offspring were collected concurrently with parent and offspring reports of adolescent internalising symptoms. Children-of-Twins structural equation models were used to control for genetic influence on the intergenerational association between parental criticism and adolescent internalising. RESULTS: Parental criticism was associated with adolescent internalising symptoms after controlling for genetic influence. No significant role was found for shared genes influencing phenotypes in both generations, although power analyses suggested that some genetic effects may have gone undetected. Models could not distinguish directionality for nongenetic, causal effects between generations. CONCLUSIONS: Parental criticism may be involved in psychosocial family processes in the context of adolescent internalising. Future studies should seek to identify these processes and provide clarity on the direction of potential causal effects.
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Padres , Gemelos , Adolescente , Humanos , Fenotipo , Suecia , Gemelos/genética , Gemelos/psicologíaRESUMEN
BACKGROUND: Self-harm is a major health concern, not only as a signal of distress but also as a strong predictor of later suicide. Self-harm can be further refined into suicidal self-harm (SSH, i.e. suicide attempt) and non-suicidal self-harm (NSSH). Understanding the aetiologies of NSSH and SSH can help inform suicide prevention strategies. Using a twin design, we investigated the phenotypic and aetiological relationships between NSSH and SSH, and their aetiological overlap with mental health problems. METHODS: We analysed data from the Twins Early Development Study using structural equation modelling. At age 21 years, 9063 twins (62.4% female) answered questions related to self-harm. At age 16 years, 19 self- or parent-reported mental health measures were administered, including measures of internalising and externalising problems, psychotic-like experiences and substance abuse. RESULTS: Prevalences for NSSH and SSH were 21.9% and 10.5%, respectively. Additive genetic factors explained half of the variance in NSSH (55%) and SSH (50%), with the rest explained by non-shared environmental factors. Phenotypically, NSSH and SSH were strongly correlated (r = 0.87) with their correlation explained by genetic (57%) and non-shared environmental (43%) factors. We found no evidence that NSSH and SSH differed in their phenotypic and aetiological relationships with mental health measures. CONCLUSION: Our findings suggest no aetiological difference between NSSH and SSH. NSSH and SSH should be regarded as two different ends of a continuum, rather than as two distinct categories.
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BACKGROUND: The rise of social media use in young people has sparked concern about the impact of cyber-victimisation on mental health. Although cyber-victimisation is associated with mental health problems, it is not known whether such associations reflect genetic and environmental confounding. METHODS: We used the co-twin control design to test the direct association between cyber-victimisation and multiple domains of mental health in young people. Participants were 7708 twins drawn from the Twins Early Development Study, a UK-based population cohort followed from birth to age 22. RESULTS: Monozygotic twins exposed to greater levels of cyber-victimisation had more symptoms of internalising, externalising and psychotic disorders than their less victimised co-twins at age 22, even after accounting for face-to-face peer victimisation and prior mental health. However, effect sizes from the most stringent monozygotic co-twin control analyses were decreased by two thirds from associations at the individual level [pooled ß across all mental health problems = 0.06 (95% CI 0.03-0.10) v. 0.17 (95% CI 0.15-0.19) in individual-level analyses]. CONCLUSIONS: Cyber-victimisation has a small direct association with multiple mental health problems in young people. However, a large part of the association between cyber-victimisation and mental health is due to pre-existing genetic and environmental vulnerabilities and co-occurring face-to-face victimisation. Therefore, preventative interventions should target cyber-victimisation in conjunction with pre-existing mental health vulnerabilities and other forms of victimisation.
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Víctimas de Crimen/psicología , Ciberacoso/psicología , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Gemelos Monocigóticos/psicología , Adulto , Víctimas de Crimen/estadística & datos numéricos , Ciberacoso/estadística & datos numéricos , Femenino , Humanos , Masculino , Medios de Comunicación Sociales , Encuestas y Cuestionarios , Reino Unido , Adulto JovenRESUMEN
BACKGROUND: Although maternal depressive symptoms are robustly associated with offspring early-life psychopathology symptoms, it is not clear which potential mechanisms are at play. We aimed to estimate the relative importance of genetic transmission and direct environmental exposure in these associations on three occasions in early childhood. METHODS: Biometric modeling of maternal sisters and their offspring from the Norwegian Mother and Child Cohort Study. The analyzed sample comprised 22 316 mothers and 35 589 offspring. Mothers reported their own depressive symptoms using the Symptom checklist, and offspring's concurrent symptoms of psychopathology using the Child Behavior Checklist at 1.5, 3, and 5 years postpartum. RESULTS: Associations between maternal symptoms of depression and offspring emotional problems were predominantly explained by passive genetic transmission at 1.5 and 3 years postpartum. At age 5, associations were more due to direct environmental exposure. For offspring behavioral problems, there was no net increase in the importance of direct environmental exposure across occasions. CONCLUSIONS: Associations between maternal depressive symptoms and offspring psychopathology symptoms remained after accounting for shared genes, consistent with a small, causal effect. For offspring emotional problems, this effect appeared to increase in importance over time. Our findings imply that treatment of maternal depressive symptoms could also benefit the offspring, and that genetic confounding should be considered in future studies of such mother-offspring associations.
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Hijo de Padres Discapacitados/psicología , Depresión/genética , Madres/psicología , Problema de Conducta/psicología , Psicopatología , Adulto , Preescolar , Femenino , Humanos , Lactante , Control Interno-Externo , Estudios Longitudinales , Masculino , Noruega , Embarazo , Factores de Riesgo , AutoinformeRESUMEN
Anxiety not only concerns mental wellbeing but also negatively impacts other areas of health. Yet, there is limited research on (a) the genetic and environmental aetiology of such relationships; (b) sex differences in aetiology and (c) non-European samples. In this study, we investigated the genetic and environmental variation and covariation of anxiety symptoms and eight components of health-related quality of life (QoL), as measured by the short form health survey (SF-36), using genetic twin model fitting analysis. Data was drawn from the Colombo Twin and Singleton Study (COTASS), a population-based sample in Sri Lanka with data on twins (N = 2921) and singletons (N = 1027). Individual differences in anxiety and QoL traits showed more shared environmental (family) effects in women. Men did not show familial effects. Anxiety negatively correlated with all eight components of QoL, mostly driven by overlapping unique (individual-specific) environmental effects in both sexes and overlapping shared environmental effects in women. This is the first study in a South Asian population supporting the association between poor mental health and reduced QoL, highlighting the value of integrated healthcare services. Associations were largely environmental, on both individual and family levels, which could be informative for therapy and intervention.
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Calidad de Vida , Gemelos , Ansiedad/genética , Enfermedades en Gemelos , Femenino , Humanos , Masculino , Sri LankaRESUMEN
Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (ß = -0.05 educational years, 95% CI -0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (ß = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers.
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Testosterona , Gemelos Dicigóticos , Estudios de Cohortes , Escolaridad , Femenino , Humanos , Masculino , Caracteres SexualesRESUMEN
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.
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Conducta Autodestructiva/genética , Anciano , Anciano de 80 o más Años , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno Bipolar/complicaciones , Trastorno Bipolar/genética , Bases de Datos como Asunto , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Humanos , Modelos Logísticos , Masculino , Análisis de la Aleatorización Mendeliana , Persona de Mediana Edad , Herencia Multifactorial/genética , Factores de Riesgo , Esquizofrenia , Conducta Autodestructiva/epidemiología , Conducta Autodestructiva/etiología , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/genética , Encuestas y Cuestionarios , Reino Unido/epidemiologíaRESUMEN
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.