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.
Read the Commentary on this article at doi: 10.1111/jcpp.13762.
Understanding how parents' cognitive and non-cognitive skills influence offspring education is essential 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 = 6407), and parent-offspring trios (N = 2534) 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 potential 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.
We investigated the relationship between childhood weight status and academic achievement across sexes and different school subjects in Norway.
We used data from the Norwegian Mother, Father and ...Child Cohort Study (MoBa), which includes genetic data (N = 13,648, 8-year-old children). We employed within-family mendelian randomization, using a body mass index (BMI) polygenic risk score as an instrument to address unobserved heterogeneity.
Contrary to most previous findings, we observed that overweight status (including obesity) has more detrimental effects on reading achievement in boys than in girls; the test scores of boys with overweight were about a standard deviation lower than those of normal weight boys, and the negative effects on reading achievement became stronger in the later grade.
Previous obesity prevention studies have mainly targeted girls, based on the assumption that the obesity penalty is greater for girls. Our findings highlight that particular attention to boys with overweight may help reduce the existing gender gap in academic achievement.
Abstract
Objective
This study investigated the associations between personality traits at age 8 and academic performance between ages 10 and 14, controlling for family confounds.
Background
Many ...studies have shown links between children’s personality traits and their school performance. However, we lack evidence on whether these associations remain after genetic and environmental confounders are accounted for.
Method
Sibling data from the Norwegian Mother and Child Cohort Study (MoBa) were used (
n
= 9701). First, we estimated the 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.
Results
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
β
= −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.
Conclusions
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.
Within-family studies typically assess indirect genetic effects of parents on children, however social support theory points to a critical role of partners and children on women's depression. To ...address this research gap and account for the high heterogeneity of depression, we calculated a general psychiatric factor using eleven major psychiatric polygenic scores (polygenic p), in up to 25,000 parent-offspring trios from the Norwegian Mother, Father and Child Cohort Study (MoBa). Multilevel modeling of trio polygenic p was used to distinguish direct and indirect genetic effects on mothers depression during pregnancy (gestational age 17 and 30 weeks), infancy (6 months, 18 months) and early childhood (3 years, 5 years, and 8 years). We found mothers polygenic p predicts their depression symptoms (b = 0.092; 95 % CI 0.087,0.098), outperforming prediction using a single major depressive disorder polygenic score (b = 0.070, 95 % CI 0.066,0.075). Jointly modeling trio polygenic p revealed indirect genetic effects of fathers (b = 0.022, 95 % CI 0.014,0.030) and children (b = 0.021, 95 % CI 0.010,0.037) on mothers' depression. Our results support the generalizability of polygenic effects across mental health and highlight the role of close family members on women's depression.
•A general factor capturing liability to any psychiatric disorder emerges using polygenic scores.•Genes for general psychiatric risk predict depression better than depression specific genes.•Indirect effects of partner and child genes influence women's depression.
Background
Children with ADHD tend to achieve less than their peers in school. It is unknown whether schools moderate this association. Nonrandom selection of children into schools related to ...variations in their ADHD risk poses a methodological problem.
Methods
We linked data on ADHD symptoms of inattention and hyperactivity and parent–child ADHD polygenic scores (PGS) from the Norwegian Mother, Father, and Child Cohort Study (MoBa) to achievement in standardised tests and school identifiers. We estimated interactions of schools with individual differences between students in inattention, hyperactivity, and ADHD‐PGS using multilevel models with random slopes for ADHD effects on achievement over schools. In our PGS analyses, we adjust for parental selection of schools by adjusting for parental ADHD‐PGS (a within‐family PGS design). We then tested whether five school sociodemographic measures explained any interactions.
Results
Analysis of up to 23,598 students attending 2,579 schools revealed interactions between school and ADHD effects on achievement. The variability between schools in the effects of inattention, hyperactivity and within‐family ADHD‐PGS on achievement was 0.08, 0.07 and 0.05 SDs, respectively. For example, the average effect of inattention on achievement was β = −0.23 (SE = 0.009), but in 2.5% of schools with the weakest effects, the value was −0.07 or less. ADHD has a weaker effect on achievement in higher‐performing schools. Schools make more of a difference to the achievements of students with higher levels of ADHD, explaining over four times as much variance in achievement for those with high versus average inattention symptoms. School sociodemographic measures could not explain the ADHD‐by‐school interactions.
Conclusions
Although ADHD symptoms and genetic risk tend to hinder achievement, schools where their effects are weaker do exist. Differences between schools in support for children with ADHD should be evened out.
Assortative mating - the non-random mating of individuals with similar traits - is known to increase trait-specific genetic variance and genetic similarity between relatives. However, empirical ...evidence is limited for many traits, and the implications hinge on whether assortative mating has started recently or many generations ago. Here we show theoretically and empirically that genetic similarity between relatives can provide evidence on the presence and history of assortative mating. First, we employed path analysis to understand how assortative mating affects genetic similarity between family members across generations, finding that similarity between distant relatives is more affected than close relatives. Next, we correlated polygenic indices of 47,135 co-parents from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and found genetic evidence of assortative mating in nine out of sixteen examined traits. The same traits showed elevated similarity between relatives, especially distant relatives. Six of the nine traits, including educational attainment, showed greater genetic variance among offspring, which is inconsistent with stable assortative mating over many generations. These results suggest an ongoing increase in familial similarity for these traits. The implications of this research extend to genetic methodology and the understanding of social and economic disparities.
Abstract
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. 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). 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. Overall, this article is intended to help the reader determine the circumstances when each method would be appropriate and why.
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.
