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Noncognitive skills such as motivation and self-regulation, predict academic achievement beyond cognitive skills. However, the role of genetic and environmental factors and of their interplay in these developmental associations remains unclear. We provide a comprehensive account of how cognitive and noncognitive skills contribute to academic achievement from ages 7 to 16 in a sample of >10,000 children from England and Wales. Results indicated that noncognitive skills become increasingly predictive of academic achievement across development. Triangulating genetic methods, including twin analyses and polygenic scores (PGS), we found that the contribution of noncognitive genetics to academic achievement becomes stronger over development. The PGS for noncognitive skills predicted academic achievement developmentally, with prediction nearly doubling by age 16, pointing to gene-environment correlation (rGE). Within-family analyses indicated both passive and active/evocative rGE processes driven by noncognitive genetics. By studying genetic effects through a developmental lens, we provide novel insights into the role of noncognitive skills in academic development.

The intergenerational transmission of educational attainment from parents to their children is one of the most important and studied relationships in social science. Longitudinal studies have found strong associations between parents’ and their children’s educational outcomes, which could be due to the effects of parents. Here we provide new evidence about whether parents’ educational attainment affects their parenting behaviours and children’s early educational outcomes using within-family Mendelian randomization and data from 40,907 genotyped parent-child trios from the Norwegian Mother, Father and Child Cohort (MoBa) study. We found evidence suggesting that parents’ educational attainment affects their children’s educational outcomes from age 5 to 14. More studies are needed to provide more samples of parent-child trios and assess the potential consequences of selection bias and grandparental effects.

Background A joint, hierarchical structure of psychopathology and personality has been reported in adults but should also be investigated at earlier ages, as psychopathology often develops before adulthood. Here, we investigate the joint factor structure of psychopathology and personality in eight-year-old children, estimate factor heritability and explore external validity through associations with established developmental risk factors. Methods Phenotypic and biometric exploratory factor analyses with bifactor rotation on genetically informative data from the Norwegian Mother, Father, and Child Cohort (MoBa) study. The analytic sub-sample comprised 10 739 children (49% girls). Mothers reported their children's symptoms of depression (Short Moods and Feelings Questionnaire), anxiety (Screen for Anxiety Related Disorders), attention-deficit/hyperactivity disorder inattention and hyperactivity, oppositional-defiant disorder, conduct disorder (Parent/Teacher Rating Scale for Disruptive Behavior Disorders), and Big Five personality (short Hierarchical Personality Inventory for Children). Developmental risk factors (early gestational age and being small for gestational age) were collected from the Medical Birth Registry. Results Goodness-of-fit indices favored a p factor model with three residual latent factors interpreted as negative affectivity, positive affectivity, and antagonism, whereas psychometric indices favored a one-factor model. ADE solutions fitted best, and regression analyses indicated a negative association between gestational age and the p factor, for both the one- and four-factor solutions. Conclusion Correlations between normative and pathological traits in middle childhood mostly reflect one heritable and psychometrically interpretable p factor, although optimal fit to data required less interpretable residual latent factors. The association between the p factor and low gestational age warrants further study of early developmental mechanisms.

Genome-wide association (GWA) studies have uncovered DNA variants associated with individual differences in general cognitive ability (g), but these are far from capturing heritability estimates obtained from twin studies. A major barrier to finding more of this ‘missing heritability’ is assessment––the use of diverse measures across GWA studies as well as time and the cost of assessment. In a series of four studies, we created a 15-min (40-item), online, gamified measure of g that is highly reliable (alpha = 0.78; two-week test-retest reliability = 0.88), psychometrically valid and scalable; we called this new measure Pathfinder. In a fifth study, we administered this measure to 4,751 young adults from the Twins Early Development Study. This novel g measure, which also yields reliable verbal and nonverbal scores, correlated substantially with standard measures of g collected at previous ages (r ranging from 0.42 at age 7 to 0.57 at age 16). Pathfinder showed substantial twin heritability (0.57, 95% CIs = 0.43, 0.68) and SNP heritability (0.37, 95% CIs = 0.04, 0.70). A polygenic score computed from GWA studies of five cognitive and educational traits accounted for 12% of the variation in g, the strongest DNA-based prediction of g to date. Widespread use of this engaging new measure will advance research not only in genomics but throughout the biological, medical, and behavioural sciences.

This study investigates associations between personality traits at age eight and academic performance between ages 10 to 14, controlling for family confounds. Sibling data from the Norwegian Mother and Child Cohort Study (MoBa) were used (n = 9,701). First, we estimated overall associations between Big Five personality traits and academic performance, including literacy, numeracy, and foreign language. Second, we added sibling fixed effects to remove unmeasured confounders shared by siblings as well as rating bias. Openness to Experience (between-person β=0.22 [95% CI 0.21 - 0.24]) and Conscientiousness (between-person β=0.18 [95% CI 0.16 - 0.20]) were most strongly related to educational performance. Agreeableness (between-person β=0.06 [95% CI -0.08 - 0.04]) and Extraversion (between-person β=0.02 [95% CI 0.00 - 0.04]) showed small associations with educational performance. Neuroticism had a moderate negative association (between-person beta=-0.14 [95% CI -0.15 - 0.11]). All associations between personality and performance were robust to confounding: the within-family estimates from sibling fixed effects models overlapped with the between-person effects. Finally, childhood personality was equally predictive of educational performance across ages and genders. Although family background is influential for academic achievement, it does not confound associations with personality. Childhood personality traits reflect unbiased and consistent individual differences in educational potential.

Distinguishing between the effects of nature and nurture constitutes a major research goal for those interested in understanding human development. It is known, for example, that many parent traits predict mental health outcomes in children, but the causal processes underlying such associations are often unclear. Family-based quasi-experimental designs such as sibling comparison, adoption and extended family studies have been used for decades to distinguish the genetic transmission of risk from the environmental effects family members potentially have on one another. Recently, these designs have been combined with genomic data, and this combination is fuelling a range of exciting methodological advances. In this review we explore these advances - highlighting the ways in which they have been applied to date and considering what they are likely to teach us in the coming years about the aetiology and intergenerational transmission of psychopathology.

A child’s environment is thought to be composed of different levels that interact with individual genetic propensities, with less advantaged environments suppressing genetic effects on achievement. However, studies have not tested this theory comprehensively across multiple environmental levels. Here, we quantify the contributions of child, parent, school, neighbourhood, district, and municipality factors to achievement, and investigate interactions between polygenic scores for educational attainment (EA-PGS) and environmental levels. We link population-wide administrative data on children’s standardised test results, schools and residential identifiers to the Norwegian Mother, Father and Child Cohort Study (MoBa), which includes >23,000 genotyped parent-child trios. We test for gene-environment interactions using multilevel models with interactions between EA-PGS and random effects for school and residential environments (thus remaining agnostic to specific features of environments) and use parent EA-PGS to control for gene-environment correlation. Our within-family results suggest that students’ EA-PGS interact with schools but not residential environments (neighbourhoods, districts, and municipalities), which explain negligible variance. Students’ EA-PGS explain four times the variance in achievement in the 2.5% of schools where EA-PGS associations are strongest as in the 2.5% where effects are weakest. Contrary to theory, PGS effects are stronger in less advantaged environments (lower-performing schools). None of the school sociodemographic measures we tested could explain the interaction. Schools make a greater difference to the achievements of students with lower EA-PGS, explaining 4% of the variance for students 2SD below the mean PGS, but 2% for students 2SD above the mean. Policy to reduce social inequality in achievement in Norway should focus on tackling unequal support across schools for children with difficulties, and not on differences between residential areas.

Background Traditionally, heritability has been estimated using family-based methods such as twin studies. Advancements in molecular genomics have facilitated the development of methods that use large samples of (unrelated or related) genotyped individuals. Methods Here, we provide an overview of common methods applied in genetic epidemiology to estimate heritability, i.e. the proportion of phenotypic variation explained by genetic variation. We provide a guide to key genetic concepts required to understand heritability estimation methods from family-based designs (twin and family studies), genomic designs based on unrelated individuals [linkage disequilibrium score regression, genomic relatedness restricted maximum-likelihood (GREML) estimation] and family-based genomic designs (sibling regression, GREML-kinship, trio-genome-wide complex trait analysis, maternal-genome-wide complex trait analysis, relatedness disequilibrium regression). Results We describe how heritability is estimated for each method and the assumptions underlying its estimation, and discuss the implications when these assumptions are not met. We further discuss the benefits and limitations of estimating heritability within samples of unrelated individuals compared with samples of related individuals. Conclusions Overall, this article is intended to help the reader determine the circumstances when each method would be appropriate and why.

Polygenic scores now explain approximately 10% of the variation in educational attainment. However, they capture not only genetic propensity but also information about the family environment. This is because of passive gene–environment correlation, whereby the correlation between offspring and parent genotypes results in an association between offspring genotypes and the rearing environment. We measured passive gene–environment correlation using information on 6,311 adoptees in the UK Biobank. Adoptees’ genotypes were less correlated with their rearing environments because they did not share genes with their adoptive parents. We found that polygenic scores were twice as predictive of years of education in nonadopted individuals compared with adoptees ( R2s = .074 vs. .037, p = 8.23 × 10−24). Individuals in the lowest decile of polygenic scores for education attained significantly more education if they were adopted, possibly because of educationally supportive adoptive environments. Overall, these results suggest that genetic influences on education are mediated via the home environment.

Background: Theoretical models of the development of childhood externalizing disorders emphasize the role of parents. Empirical studies have not been able to identify specific aspects of parental behaviors explaining a considerable proportion of the observed individual differences in externalizing problems. The problem is complicated by the contribution of genetic factors to externalizing problems, as parents provide both genes and environments to their children. We studied the joint contributions of direct genetic effects of children and the indirect genetic effects of parents through the environment on externalizing problems. Methods: The study used genome-wide single nucleotide polymorphism data from 9,675 parent–offspring trios participating in the Norwegian Mother Father and child cohort study. Based on genomic relatedness matrices, we estimated the contribution of direct genetic effects and indirect maternal and paternal genetic effects on ADHD, conduct and disruptive behaviors at 8 years of age. Results: Models including indirect parental genetic effects were preferred for the ADHD symptoms of inattention and hyperactivity, and conduct problems, but not oppositional defiant behaviors. Direct genetic effects accounted for 11% to 24% of the variance, whereas indirect parental genetic effects accounted for 0% to 16% in ADHD symptoms and conduct problems. The correlation between direct and indirect genetic effects, or gene–environment correlations, decreased the variance with 16% and 13% for conduct and inattention problems, and increased the variance with 6% for hyperactivity problems. Conclusions: This study provides empirical support to the notion that parents have a significant role in the development of childhood externalizing behaviors. The parental contribution to decrease in variation of inattention and conduct problems by gene–environment correlations would limit the number of children reaching clinical ranges in symptoms. Not accounting for indirect parental genetic effects can lead to both positive and negative bias when identifying genetic variants for childhood externalizing behaviors. publishedVersion

Background\udGeneralized anxiety and depression are extremely prevalent and debilitating. There is evidence for age and sex variability in symptoms of depression, but despite comorbidity it is unclear whether this extends to anxiety symptomatology. Studies using questionnaire sum scores typically fail to address this phenotypic complexity.\ud\udMethod\udWe conducted exploratory and confirmatory factor analyses on Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) items to identify latent factors of anxiety and depression in participants from the Genetic Links to Anxiety and Depression Study (N = 35,637; 16–93 years). We assessed age- and sex-related variability in latent factors and individual symptoms using multiple logistic regression.\ud\udResults\udFour factors of mood, worry, motor, and somatic symptoms were identified (comparative fit index [CFI] = 0.99, Tucker–Lewis Index [TLI] = 0.99, root mean square error of approximation [RMSEA] = 0.07, standardized root mean square residuals [SRMR] = 0.04). Symptoms of irritability (odds ratio [OR] = 0.81) were most strongly associated with younger age, and sleep change (OR = 1.14) with older age. Males were more likely to report mood and motor symptoms (p

Similarities between parents and offspring arise from nature and nurture. Beyond this simple dichotomy, recent genomic studies have uncovered "genetic nurture" effects, whereby parental genotypes influence offspring outcomes via environmental pathways rather than genetic transmission. Such genetic nurture effects also need to be accounted for to accurately estimate "direct" genetic effects (i.e., genetic effects on a trait originating in the offspring). Empirical studies have indicated that genetic nurture effects are particularly relevant to the intergenerational transmission of risk for child educational outcomes, which are, in turn, associated with major psychological and health milestones throughout the life course. These findings have yet to be systematically appraised across contexts. We conducted a systematic review and meta-analysis to quantify genetic nurture effects on educational outcomes. A total of 12 studies comprising 38,654 distinct parent(s)-offspring pairs or trios from 8 cohorts reported 22 estimates of genetic nurture effects. Genetic nurture effects on offspring's educational outcomes (βgenetic nurture = 0.08, 95% CI [0.07, 0.09]) were smaller than direct genetic effects (βdirect genetic = 0.17, 95% CI [0.13, 0.20]). Findings were largely consistent across studies. Genetic nurture effects originating from mothers and fathers were of similar magnitude, highlighting the need for a greater inclusion of fathers in educational research. Genetic nurture effects were largely explained by observed parental education and socioeconomic status, pointing to their role in environmental pathways shaping child educational outcomes. Findings provide consistent evidence that environmentally mediated parental genetic influences contribute to the intergenerational transmission of educational outcomes, in addition to effects due to genetic transmission.

Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30-60%. We conducted a genome-wide association study of Lifetime Anxiety Disorder (n = 83 565) and an additional Current Anxiety Symptoms (n= 77 125) analysis. The liability scale common variant heritability estimate for Lifetime Anxiety Disorder was 26%, and for Current Anxiety Symptoms was 31%. Five novel genome-wide significant loci were identified including an intergenic region on chromosome 9 that has previously been associated with neuroticism, and a locus overlapping the BDNF receptor gene, NTRK2. Anxiety showed significant genetic correlations with depression and insomnia as well as coronary artery disease, mirroring findings from epidemiological studies. We conclude that common genetic variation accounts for a substantive proportion of the genetic architecture underlying anxiety.

Background: Diverse behaviour problems in childhood correlate phenotypically, suggesting a general dimension of psychopathology that has been called the p factor. The shared genetic architecture between childhood psychopathology traits also supports a genetic p. This study systematically investigates the manifestation of this common dimension across self‐, parent‐ and teacher‐rated measures in childhood and adolescence. / Methods: The sample included 7,026 twin pairs from the Twins Early Development Study (TEDS). First, we employed multivariate twin models to estimate common genetic and environmental influences on p based on diverse measures of behaviour problems rated by children, parents and teachers at ages 7, 9, 12 and 16 (depressive traits, emotional problems, peer problems, autism traits, hyperactivity, antisocial behaviour, conduct problems and psychopathic tendencies). Second, to assess the stability of genetic and environmental influences on p across time, we conducted longitudinal twin modelling of the first phenotypic principal components of childhood psychopathological measures across each of the four ages. Third, we created a genetic p factor in 7,026 unrelated genotyped individuals based on eight polygenic scores for psychiatric disorders to estimate how a general polygenic predisposition to mostly adult psychiatric disorders relates to childhood p. / Results: Behaviour problems were consistently correlated phenotypically and genetically across ages and raters. The p factor is substantially heritable (50%–60%) and manifests consistently across diverse ages and raters. However, residual variation in the common factor models indicates unique contributions as well. Genetic correlations of p components across childhood and adolescence suggest stability over time (49%–78%). A polygenic general psychopathology factor derived from studies of psychiatric disorders consistently predicted a general phenotypic p factor across development (0.3%–0.9%). / Conclusions: Diverse forms of psychopathology generally load on a common p factor, which is highly heritable. There are substantial genetic influences on the stability of p across childhood. Our analyses indicate genetic overlap between general risk for psychiatric disorders in adulthood and p in childhood, even as young as age 7. The p factor has far‐reaching implications for genomic research and, eventually, for diagnosis and treatment of behaviour problems. /

Background Children who consistently withdraw from social situations face increased risk for later socioemotional difficulties. Twin studies indicate that genetic factors substantially account for the persistence of social withdrawal over time. However, the molecular genetic etiology of chronic courses of social wariness and preference for solitude, two dimensions of social withdrawal, remains undocumented. The objectives of the present study were (a) to identify high-risk trajectories for social wariness and preference for solitude in childhood and (b) to examine whether falling on these high-risk trajectories can be predicted by specific polygenic scores for mental health traits and disorders and by a general polygenic predisposition to these traits. Methods Teachers evaluated 971 genotyped children at five occasions (age 6 to 12 years) from two prospective longitudinal studies, the Quebec Newborn Twin Study and the Quebec Longitudinal Study of Child Development. Developmental trajectories for social wariness and preference for solitude were identified. We tested whether polygenic scores for attention deficit hyperactivity disorder, autism spectrum disorder, depression, loneliness, and subjective well-being, as well as a general mental health genetic risk score derived across these traits, were associated with the developmental trajectories. Results Polygenic scores differentially predicted social wariness and preference for solitude. Only the loneliness polygenic score significantly predicted the high trajectory for social wariness. By contrast, the general mental health genetic risk score factor was associated with the trajectory depicting high-chronic preference for solitude. Conclusions Distinct associations were uncovered between the polygenic scores, social wariness, and preference for solitude.

Estimates from genome-wide association studies (GWAS) represent a combination of the effect of inherited genetic variation (direct effects), demography (population stratification, assortative mating) and genetic nurture from relatives (indirect genetic effects). GWAS using family-based designs can control for demography and indirect genetic effects, but large-scale family datasets have been lacking. We combined data on 159,701 siblings from 17 cohorts to generate population (between-family) and within-sibship (within-family) estimates of genome-wide genetic associations for 25 phenotypes. We demonstrate that existing GWAS associations for height, educational attainment, smoking, depressive symptoms, age at first birth and cognitive ability overestimate direct effects. We show that estimates of SNP-heritability, genetic correlations and Mendelian randomization involving these phenotypes substantially differ when calculated using within-sibship estimates. For example, genetic correlations between educational attainment and height largely disappear. In contrast, analyses of most clinical phenotypes (e.g. LDL-cholesterol) were generally consistent between population and within-sibship models. We also report compelling evidence of polygenic adaptation on taller human height using within-sibship data. Large-scale family datasets provide new opportunities to quantify direct effects of genetic variation on human traits and diseases.

Non-random mating by assortment on heritable traits can have consequences for the genetic resemblance between siblings and in-laws in succeeding generations. We studied polygenic scores and phenotypic data from pairs of partners (26,681), siblings (2,170), siblings-in-law (3,905), and siblings-co-in-law (1,763) in the Norwegian Mother, Father and Child Cohort Study. Using structural equation models, we estimated associations between latent genetic and phenotypic variables without measurement error. We found evidence of genetic similarity between partners for educational attainment (rg=0.37), height (rg=0.13), and depression (rg=0.03). Common genetic variants related to educational attainment correlated between siblings above 0.50 (rg=0.68) and between siblings-in-law (rg=0.25) and siblings-co-in-law (rg=0.09). There was indirect assortment on proxy traits for education and depression but not height. Comparisons between the genetic similarities of partners and siblings indicated that genetic variances were in intergenerational equilibrium. This study shows that assortative mating has influenced the genetic structure of extended families for several generations.

The present study examined, within a longitudinal family-informed design and across middle childhood, the predictive associations between preference for solitude and social wariness, two forms of social withdrawal, and peer difficulties. Specifically, preference for solitude, rather than social wariness, was expected to predict peer victimization and rejection, two aspects of peer difficulties. A total of 1,014 children from the Quebec Newborn Twin Study were assessed by teachers and peers at ages 6, 7, and 10 years. Multilevel analyses conducted across three levels, between family, within family, and within person, revealed that preference for solitude, rather than social wariness, increased the risk for peer difficulties in terms of both peer victimization and peer rejection. Specifically, preference for solitude was systematically associated with peer rejection starting at age 6 years and became progressively associated with peer victimization over time. This pattern was found both between and within families. In addition, the predictive association with peer rejection was found within genetically identical, monozygotic twin pairs, suggesting that this predictive association existed after taking into account genetic vulnerabilities. Social wariness was systematically unrelated to peer difficulties. These findings suggest that preference for solitude, rather than social wariness, is a risk factor for peer difficulties. They underscore the relevance of distinguishing these dimensions of social withdrawal and illustrate the usefulness of a family-informed design to document the processes underlying childhood social adjustment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Child educational development is associated with major psychological, social, economic and health milestones throughout the life course. Understanding the early origins of educational inequalities and their reproduction across generations is therefore crucial. Recent genomic studies provide novel insights in this regard, uncovering “genetic nurture” effects, whereby parental genotypes influence offspring’s educational development via environmental pathways rather than genetic transmission. These findings have yet to be systematically appraised. We conducted the first systematic review and meta-analysis to quantify genetic nurture effects on educational outcomes and investigate key moderators. Twelve studies comprising 38,654 distinct parent(s)-offspring pairs or trios from eight cohorts were included, from which we derived 22 estimates of genetic nurture effects. Multilevel random effects models showed that the effect of genetic nurture on offspring’s educational outcomes (βgenetic nurture = 0.08, 95% CI [0.07, 0.09]) was about half the size of direct genetic effects (βdirect genetic = 0.17, 95% CI [0.13, 0.20]). Maternal and paternal genetic nurture effects were similar in magnitude, suggesting comparable roles of mothers and fathers in determining their children’s educational outcomes. Genetic nurture effects were largely explained by parental educational level and family socioeconomic status, suggesting that genetically influenced environments play an important role in shaping child educational outcomes. Even after accounting for genetic transmission, we provide evidence that environmentally mediated parental genetic influences contribute to the intergenerational transmission of educational outcomes. Further exploring these downstream environmental pathways may inform educational policies aiming to break the intergenerational cycle of educational underachievement and foster social mobility.Public Significance StatementThis meta-analysis demonstrates that parents’ genetics influence their children’s educational outcomes through the rearing environments that parents provide. This “genetic nurture” effect is largely explained by family socioeconomic status and parental education level, is similar for mothers and fathers (suggesting that both parents equally shape their children’s educational outcomes) and is about half the size of direct genetic effects on children’s educational outcomes. Interventions targeting such environmental pathways could help to break the intergenerational cycle of educational underachievement and foster social mobility.

Background. Children who consistently withdraw from social situations face increased risk for later socioemotional difficulties. Twin studies indicate that genetic factors account for a substantial share in the persistence of social withdrawal over time. However, the molecular genetic etiology of chronic courses of social wariness and preference for solitude, two dimensions of social withdrawal, remain unexplored. The objectives were 1) to identify high-risk trajectories for social wariness and preference for solitude in the childhood years, and 2) to examine whether the assignment to these high-risk trajectories can be predicted by polygenic scores for mostly adult mental health traits and disorders and by a general polygenic predisposition to these traits. Methods. Teachers evaluated 1133 genotyped children at five occasions (age 6 to 12 years) from two prospective longitudinal studies, the Quebec Newborn Twin Study and the Quebec Longitudinal Study of Child Development. Developmental trajectories for social wariness and preference for solitude were identified. We tested whether polygenic scores for attention deficit hyperactivity disorder, autism spectrum disorder, depression, loneliness and subjective well-being, as well as a general mental health genetic risk score derived across these traits were associated with the developmental trajectories. Results. Polygenic scores differently predicted social wariness and preference for solitude. Only the loneliness polygenic score significantly predicted the elevated trajectory for social wariness. By contrast, the general mental health genetic risk score factor was associated with the trajectory depicting high and chronic preference for solitude. Conclusion. Distinct associations were uncovered between the polygenic scores, social wariness, and preference for solitude. These results point to multiple genetic processes underlying the development of social withdrawal, as well as the potential value of preference for solitude as an endophenotype for the later onset and persistence of mental health difficulties in adulthood.

The relationship between genetic and environmental risk is complex and for many traits, estimates of genetic effects may be inflated by passive gene-environment correlation. This arises because biological offspring inherit both their genotypes and rearing environment from their parents. We tested for passive gene-environment correlation in adult body composition traits using the ‘natural experiment’ of childhood adoption, which removes passive gene-environment correlation within families. Specifically, we compared 6165 adoptees with propensity score matched non-adoptees in the UK Biobank. We also tested whether passive gene-environment correlation inflates the association between psychiatric genetic risk and body composition. We found no evidence for inflation of heritability or polygenic scores in non-adoptees compared to adoptees for a range of body composition traits. Furthermore, polygenic risk scores for anorexia nervosa, attention-deficit/hyperactivity disorder and schizophrenia did not differ in their influence on body composition traits in adoptees and non-adoptees. These findings suggest that passive gene-environment correlation does not inflate genetic effects for body composition, or the influence of psychiatric disorder genetic risk on body composition. Our design does not look at passive gene-environment correlation in childhood, and does not test for ‘pure’ environmental effects or the effects of active and evocative gene-environment correlations, where child genetics directly influences home environment. However, these findings suggest that genetic influences identified for body composition in this adult sample are direct, and not confounded by the family environment provided by biological relatives. Electronic supplementary material The online version of this article (10.1007/s10519-020-10028-6) contains supplementary material, which is available to authorized users.

Background Children of parents with high levels of neuroticism tend to have high neuroticism themselves as well as increased risk of experiencing symptoms of anxiety and depression. It is not yet clear how much of this link is attributable to a potential effect of parent on child (e.g., via a socializing effect) versus to shared genetic risk. We aimed to determine whether there is an intergenerational association after accounting for genetic transmission and assortative mating. Methods We used data from the Norwegian Mother, Father and Child Cohort Study including 11,088 sibling pairs in the parental generation, their partners (N = 22,176) and their offspring (N = 26,091). Exposures were maternal and paternal neuroticism (self‐reported), and the outcomes were neuroticism, symptoms of depression, and symptoms of anxiety in 8‐year‐old children (mother‐reported). Results After accounting for assortative mating in parents (phenotypic r = 0.26) and genetic transmission (explaining 0%–18% of the mother‐offspring correlations), potential maternal effects explained 80% (95% CI = 47–95) of the association with offspring neuroticism (mother‐child r = 0.31), 78% (95% CI = 66–89) of the association with offspring depressive symptoms (r = 0.31), and 98% (95% CI = 45–112) of the association with offspring anxiety symptoms (r = 0.16). Intergenerational transmission of genetic variants associated with paternal neuroticism accounted for ∼40% (CI = 22%–58%) of the father‐offspring correlations with neuroticism and symptoms of depression (r = 0.13 and 0.13, respectively) but none with offspring symptoms of anxiety (r = 0.05). The remaining father‐offspring correlations were explained by maternal influences through assortative mating. Conclusions These results are consistent with direct effects between maternal and offspring neuroticism and between maternal neuroticism and offspring symptoms of anxiety and depression. Further understanding of these intergenerational processes will require an adequate model of how these constructs (neuroticism, anxiety and depression) relate to each other within generations.

Understanding how parents’ cognitive and non-cognitive skills influence offspring education is vital for educational, family and economic policy. We use genetics (GWAS-by-subtraction) to assess a latent, broad non-cognitive skills dimension. To index parental effects controlling for genetic transmission, we estimate indirect parental genetic effects of polygenic scores on childhood and adulthood educational outcomes, using siblings (N=47,459), adoptees (N=6,407), and parent-offspring trios (N=2,534) in three UK and Dutch cohorts. We find that parental cognitive and non-cognitive skills affect offspring education through their environment: on average across cohorts and designs, indirect genetic effects explain 36-40% of population polygenic score associations. However, indirect genetic effects are lower for achievement in the Dutch cohort, and for the adoption design. We identify causes of higher sibling- and trio-based estimates: prenatal indirect genetic effects, population stratification, and assortative mating. Our phenotype-agnostic, genetically sensitive approach has established overall environmental effects of parents’ skills, facilitating future mechanistic work.

Background Anxiety and depressive disorders can be chronic and disabling. Although there are effective treatments, only a fraction of those impaired receive treatment. Predictors of treatment-seeking and treatment receipt could be informative for initiatives aiming to tackle the burden of untreated anxiety and depression. Aims To investigate sociodemographic characteristics associated with treatment-seeking and treatment receipt. Method Two binary retrospective reports of lifetime treatment-seeking (n = 44 810) and treatment receipt (n = 37 346) were regressed on sociodemographic factors (age, gender, UK ethnic minority background, educational attainment, household income, neighbourhood deprivation and social isolation) and alternative coping strategies (self-medication with alcohol/drugs and self-help) in UK Biobank participants with lifetime generalised anxiety or major depressive disorder. Analyses were also stratified by gender. Results Treatment access was more likely in those who reported use of self-help strategies, with university-level education and those from less economically advantaged circumstances (household income £100 000). Men who self-medicated and/or had a vocational qualification were also less likely to seek treatment. Conclusions This work on retrospective reports of treatment-seeking and treatment receipt at any time of life replicates known associations with treatment-seeking and treatment receipt during time of treatment need. More work is required to understand whether improving rates of treatment-seeking improves prognostic outcomes for individuals with anxiety or depression.

BACKGROUND: In England, all state-funded schools are inspected by an independent government agency, the Office for Standards in Education, Children's Services and Skills (Ofsted). Inspections aim to hold schools accountable and to promote the improvement of education, with the results made available to the public. Ofsted reports intend to index school quality, but their influence on students' individual outcomes has not been previously studied. The aim of the current study was to explore the extent to which school quality, as indexed by Ofsted ratings, is associated with students' educational achievement, well-being and school engagement. METHODS: We use an England population-based sample of 4,391 individuals, for whom school performance at age 11 and GCSE grades at age 16 were accessed from the National Pupil Database, and who completed measures of well-being and school engagement at age 16. RESULTS: We found that Ofsted ratings of secondary school quality accounted for 4% of the variance in students' educational achievement at age 16, which was further reduced to 1% of the variance after we accounted for prior school performance at age 11 and family socioeconomic status. Furthermore, Ofsted ratings were weak predictors of school engagement and student well-being, with an average correlation of .03. CONCLUSION: Our findings suggest that differences in school quality, as indexed by Ofsted ratings, have little relation to students' individual outcomes. Accordingly, our results challenge the usefulness of Ofsted ratings as guides for parents and students when choosing secondary schools.

Background: Children of parents with high levels of neuroticism tend to have high neuroticism themselves, as well as increased risk of experiencing symptoms of anxiety and depression. It is not yet clear how much of this link is attributable to a potential effect of parent on child (e.g., via a socializing effect) vs. to shared genetic risk. Methods: This study is based on data from the Norwegian Mother, Father and Child Cohort Study. We used data from 11,088 sibling pairs in the parental generation, their partners (N= 22,176), and their offspring (N=26,091). Exposures were maternal and paternal neuroticism (self-reported), and the outcomes were neuroticism, symptoms of depression, and symptoms of anxiety in 8-year-old children (mother-reported). Outcomes: After accounting for assortative mating in parents (phenotypic r=0.26), genetic transmission of maternal neuroticism accounted for 16% of the correlation with offspring neuroticism (mother-child r=0.31), 18% of the association with offspring depressive symptoms (r=0.31), and 0% of the association with offspring anxiety symptoms (r=0.16). Intergenerational transmission of genes associated with paternal neuroticism accounted for ~40% of the father-offspring correlations with neuroticism and symptoms of depression (r=0.13 and 0.13, respectively) but none with offspring symptoms of anxiety (r=0.05). The remaining father-offspring correlations was explained by maternal influences through assortative mating. Interpretations: These results are consistent with direct effects between maternal and offspring neuroticism and between maternal neuroticism and offspring symptoms of anxiety and depression, suggesting that interventions targeted at family functioning could benefit the children. Funding Statement: This work was supported by the Research Council of Norway (RCN) (262177). E.M.E. and L.C.G. were funded by the RCN (262177). E.Y. was funded by the RCN (288083 and 262177). A.H. was supported by the South-Eastern Norway Regional Health Authority (2018059 and 2020022). T.A.McA. was supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (107706/Z/15/Z) and the RCN (288083). L.J.H. was supported by funding from the SouthEastern Norway Regional Health Authority (2018058). F.A.T. was supported by the RCN (300668). This work was partly supported by the RCN through its Centres of Excellence funding scheme, project number 262700. Declaration of Interests: The authors have declared that they have no competing or potential conflicts of interest. Ethics Approval Statement: The establishment of MoBa and initial data collection was based on a license from the Norwegian Data protection agency and approval from The Regional Committees for Medical and Health Research Ethics. The MoBa cohort is based on regulations based on the Norwegian Health Registry Act. The current study was approved by The Regional Committees for Medical and Health Research Ethics.

Twin studies have shown that emotional problems (anxiety and depression) in childhood and adolescence are moderately heritable (~20–50%). In contrast, DNA-based ‘SNP heritability’ estimates are generally

There is growing interest in interoception, the perception of the body’s internal state, and its relevance for health and higher-order cognition across development. To date, most evidence linking interoception to health and cognition has used the heartbeat counting task. However, the stability of the measure across time, particularly during childhood, and the etiological factors that underlie individual differences in stability remain largely unexamined. Using data from the ECHO twin sample (N=204 twin pairs), we estimated the magnitude of genetic and environmental influences on the stability of heartbeat counting across a two-year period (8-10 years), the longest time-frame examined. We found a relatively modest correlation between heartbeat counting accuracy across time (r=.35), with accuracy on the heartbeat counting task improving with age. In our longitudinal twin analysis, we found that the heritability of heartbeat counting dropped between Time 1 and Time 2 from 30% to 6%. No new genetic influences were observed at Time 2, suggesting that genetic influences across this age-range are entirely stable. In contrast, shared environmental influences increased from 6% to 22%, with most of the influence at Time 2 due to new environmental factors. Of note, nonshared environmental factors accounted for the greatest proportion of variance at both time points, 64% and 73% respectively, and were the main contributors to temporal stability in heartbeat counting accuracy. Future research should seek to identify these non-shared environmental factors and elucidate whether this relatively modest stability reflects variability of interoception across development or unreliability of the heartbeat counting task.

Background. Anxiety and depressive disorders can be classified under a bi-dimensional model, where depression and generalized anxiety disorder are represented by distress and the other anxiety disorders, by fear. The phenotypic structure of this model has been validated, but twin studies only show partial evidence for genetic and environmental distinctions between distress and fear. Moreover, the effects of genetic variants are mostly shared between anxiety and depression, but the genome-wide genetic distinction between distress and fear remain unexplored. This study aimed to examine the degree of common genetic variation overlap between distress and fear, and their associations with the psychosocial risk factors of loneliness and social isolation. Methods. We used genome-wide data from 157,366 individuals in the UK Biobank who answered a mental health questionnaire. Results. Genetic correlations indicated that depression and generalized anxiety had a substantial genetic overlap, and that they were genetically partially distinct from fear disorders. Associations with loneliness, but not social isolation, showed that loneliness was more strongly associated with both distress disorders than with fear. Conclusions. Our findings shed light on genetic and environmental mechanisms that are common and unique to distress and fear and contribute to current knowledge on individuals’ susceptibility to anxiety and depression.

Individual-level polygenic scores can now explain ∼10% of the variation in number of years of completed education. However, associations between polygenic scores and education capture not only genetic propensity but information about the environment that individuals are exposed to. This is because individuals passively inherit effects of parental genotypes, since their parents typically also provide the rearing environment. In other words, the strong correlation between offspring and parent genotypes results in an association between the offspring genotypes and the rearing environment. This is termed passive gene-environment correlation. We present an approach to test for the extent of passive gene-environment correlation for education without requiring intergenerational data. Specifically, we use information from 6311 individuals in the UK Biobank who were adopted in childhood to compare genetic influence on education between adoptees and non-adopted individuals. Adoptees’ rearing environments are less correlated with their genotypes, because they do not share genes with their adoptive parents. We find that polygenic scores are twice as predictive of years of education in non-adopted individuals compared to adoptees (R2= 0.074 vs 0.037, difference test p= 8.23 × 10−24). We provide another kind of evidence for the influence of parental behaviour on offspring education: individuals in the lowest decile of education polygenic score attain significantly more education if they are adopted, possibly due to educationally supportive adoptive environments. Overall, these results suggest that genetic influences on education are mediated via the home environment. As such, polygenic prediction of educational attainment represents gene-environment correlations just as much as it represents direct genetic effects.