Yasmin Iona Ahmadzadeh

Parenting behaviours are often linked to childhood aggression, but many studies fail to account for shared genetics or test directionality. Using family-based designs, we control for genetic confounding and examined bidirectional effects across two samples. First, we apply a children-of-twins/siblings design in the Norwegian Mother Father and Child Cohort Study which uses genetic relatedness between family members to separate genetic and environmental components of parent-child associations. Second, we use longitudinal models in the USA-based Early Growth and Development Study, an adoption sample where parents and child are not genetically related, enabling estimation of parent-child associations without genetic confounding. Across both studies, we find evidence for genetic and environmental transmission between parenting and child aggression. We show significant child-to-parent effects on inconsistent discipline in both samples. In the children-of-twins analysis, the association between positive parenting and child aggression is shown to be due to shared genetics, where no statistically significant association is observed in the adoption sample. These findings build on the growing body of literature showing genetic influences on both aggression and parenting behaviours, whilst underscoring the value of triangulation.

High or persistent levels of aggression are associated with psychopathology and difficulties with health and education as the child develops. Parenting behaviours have been frequently associated with childhood aggression, however much of this literature does not control for the shared genetics between parent and child or investigate the direction of effects. Here, we triangulated across two family-based designs, the Norwegian Mother Father and Child Cohort Study (MoBa) and the Early Growth and Development Study (EGDS) from the United States, both of which have comparable measures and allow for direction-of-causation analysis and control for shared genetics. Analyses were pre-registered.We found converging evidence across both studies for both genetic and environmental transmission in the relationship between parenting behaviours and child aggressive behaviour, with the association between positive parenting and lower child aggression being driven primarily by shared genetics. In MoBa, 47% of the association between inconsistent parenting and child aggression was explained by shared genetics. We found significant child-to-parent effects in both the MoBa and the EGDS samples. This work shows the strength of triangulation, allowing us to describe a pattern of intergenerational association that is not dependent on a specific sample or study design.

Background: Genetic variants in family members may exert environmentally mediated indirect genetic effects on children’s attention-deficit hyperactivity disorder (ADHD) traits. We set out to quantify the indirect genetic effects of parents’ genotypes on children’s ADHD traits as measured in early and mid-childhood. Methods: We analyzed data from genotyped trios of children, mothers, and fathers of European ancestry from the Norwegian Mother, Father and Child Cohort Study (MoBa) birth cohort. Child ADHD data were available for analytic subsamples of 12,374 trios at age 5 (children 50.5% male), and 12,714 trios at age 8 (children 50.9% male). We quantified direct genetic effects of children’s genotype and indirect effects of mothers’ and fathers’ genotypes on children’s ADHD traits at each age. Results: At age 5, maternal indirect genetic effects explained roughly twice as much variance in children’s ADHD traits as did child direct genetic effects. At age 8, maternal indirect genetic effects and child direct genetic effects explained roughly equal portions of variance in child ADHD traits. However, issues with power were evident throughout analyses and precluded confident interpretation of indirect genetic effects. Conclusions: We find tentative evidence for heritable parental traits exerting environmental effects on child ADHD traits in early and mid-childhood, suggesting that maternal genotypes exert indirect effects on children’s traits after accounting for the direct effects of children’s own genotype. However, future studies with larger samples are needed to enable clear inferences on the importance of indirect genetic effects for children’s ADHD traits.

Background: Children diagnosed with ADHD and other comorbid mental health conditions often exhibit more severe functional impairments than those without comorbid conditions, including a tendency for their ADHD symptoms to persist into later developmental stages. We conducted a systematic review and quantitative analysis to investigate the extent to which specific childhood comorbidities (internalizing, externalizing and neurodevelopmental conditions) predict the persistence of childhood ADHD into later developmental stages. Methods: We extracted data from 26 studies meeting the criteria for inclusion and applied multilevel random effects models to obtain pooled estimates of Cohen's d for selected predictors on ADHD persistence. Results: Childhood comorbid internalizing and externalizing conditions ( d = 0.19 and d = 0.31, respectively), but not neurodevelopmental disorders, were significantly associated with ADHD persistence. After adjusting for covariates (sex, age and other comorbidities), this association diminished for externalizing conditions ( d _adj = 0.24) and was no longer significant for internalizing conditions ( d _adj = 0.06). The association between comorbid externalizing behavior problems and ADHD persistence was found only in studies that used parent‐reported data to measure childhood ADHD and externalizing conditions, but not in studies that included teacher‐reported childhood symptoms. Conclusions: Childhood comorbid externalizing and, to a lesser extent, internalizing conditions were associated with the persistence of ADHD, but this association may be partially due to confounders. Childhood comorbidity of neurodevelopmental disorders does not appear to increase the likelihood of ADHD persistence.

Prediction from polygenic scores may be confounded by sources of passive gene-environment correlation (rGE; e.g. population stratification, assortative mating, and environmentally mediated effects of parental genotype on child phenotype). Using genomic data from 10 000 twin pairs, we asked whether polygenic scores from the most recent externalising genome-wide association study predict conduct problems, ADHD symptomology and callous-unemotional traits, and whether these predictions are biased by rGE. We ran regression models including within-family and between-family polygenic scores, to separate the direct genetic influence on a trait from environmental influences that correlate with genes (indirect genetic effects). Findings suggested that this externalising polygenic score is a good index of direct genetic influence on conduct and ADHD-related symptoms across development, with minimal bias from rGE, although the polygenic score predicted less variance in CU traits. Post-hoc analyses showed some indirect genetic effects acting on a common factor indexing stability of conduct problems across time and contexts.

Background: Almost one in five (18.8%) UK adolescents are estimated to self‐harm and many young people initiate self‐harm early (average age 13 years). Prevention of self‐harm should be informed by knowledge about risk factors (e.g. socio‐demographic indices), characteristics (i.e. motivation for self‐harm and help‐seeking behaviours), as well as relative aetiological genetic and environmental processes. Previous twin studies evidence both genetic and environmental influences on self‐harm. However, to date, there has been no genetically informed research on self‐harm aetiology across development, nor studies identifying risk factors for initiating self‐harm at a younger age. Methods: We examined self‐harm in the Twins Early Development Study, a birth cohort twin study. Using clustered regression models, we tested associations of socio‐demographic factors and victimisation with lifetime self‐harm and age of self‐harm initiation, both reported at 21. To investigate stability and/or change in genetic and environmental influences on self‐harm we interpreted a multivariate Cholesky decomposition across ages ≤16, 21, and 26. Results: Self‐harm was more common in adolescence than early adulthood, and the incidence of self‐harm in early adulthood was low (1.4%). The most common motivation for self‐harm was ‘to get relief from a terrible state of mind’ (83.4%). Independent predictors of self‐harm and earlier initiation of self‐harm were being female, belonging to a gender and/or sexual minority group, and experience of bullying victimisation. Sexual minority status was still significantly associated with self‐harm after controlling for familial factors in co‐twin control analyses. The Cholesky decomposition showed stability in genetic influences and innovation in non‐shared environmental influences on self‐harm. Conclusions: Adolescence should be a key period for self‐harm interventions. Women, sexual, and gender minorities, and those experiencing victimisation may need targeted support early in adolescence. Furthermore, it should be acknowledged that different individuals can be at risk at different stages as environmental factors influencing self‐harm change across time.

Background: Gene-environment interaction is likely to contribute to human development, but individual effects are difficult to detect, especially for behavioural outcomes. Genetic variants associated with phenotypic variability (i.e. those with heteroscedastic effects) are potential candidates for tests of interaction. We conduct the first study estimating genetic effects on phenotypic variability in childhood behavioural traits. Methods: We used item response theory models to reduce measurement error in 71 behavioural traits across childhood (ages 6 months - 14 years) in the Norwegian Mother, Father and Child Birth Cohort Study (MoBa; NMEAN: 31,614; NMAX: 58,833) and subsequently tested for genome-wide association (GWA) of mean and variance effects. Downstream analyses included phenome-wide association analyses of independently associated loci, estimation of SNP-based heritability and genetic correlation, and polygenic score analysis in an independent sample, the Twins Early Development Study (NMEAN=1,837). All analyses were repeated in anthropometric traits, to compare with analyses of behaviour. Results: Across the 71 behavioural phenotypes, there were 17 independent genetic variants associated with phenotypic variability, and 44 associated with mean levels. Genome-wide variance effects explained up to 9.7% of the variance (mean h2vGWA=1.8%), whereas mean effects explained up to 15.8% of the phenotypic variance (mean h2GWA=6.0%). In comparison, for anthropometric traits variance effects explained up to 6.7% of the variance in phenotypic variability (mean h2vGWA=2.1%), and mean effects explained up to 42.7% of the phenotypic variance (mean h2GWA=30.5%). There was little evidence that higher variance-based polygenic scores were associated with greater phenotypic variance, or for vPGS-by-environment interactions. Discussion: In keeping with previous analyses of genetic effects on trait variability in anthropometric and biomarker traits, there were fewer variance effects than mean effects for behavioural traits. Nonetheless, several SNPs with effects on phenotypic variance were identified for follow-up analyses. Standard GWA and PGS analyses require large samples. It is likely that even larger samples will be required to comprehensively detect variance effects involved in childhood behaviour. We have provided an extensive summary of the phenotypes assessed in MoBa accompanied by GWA summary statistics made available for future GWA meta-analyses of childhood behavioural traits.

Background: Experiences of racism are linked to negative physical and mental health outcomes among those exposed. According to quantitative research derived mainly from the United States, these negative outcomes can have cascading effects in families, when parents' experiences of racism indirectly impact offspring. New research is warranted for families in the United Kingdom, informed by a qualitative approach to canvassing community knowledge and perspectives, exploring how existing findings relate to lived experiences. Method: We conducted four online focus groups with 14 parents of school‐aged children and 14 adolescents who had experienced racism in the United Kingdom. Participants were asked what children know of parents' experiences of racism, and how these experiences can impact parent–child interactions, mental health and well‐being. Focus group recordings were transcribed, data coded and analysed through iterative categorisation. Results: Analyses drew four themes from participants' insights. Together, themes illuminated the pervasive nature of racism experienced by some families in the United Kingdom. Parent and child experiences of racism were connected and co‐occurring, with indirect effects impacting mental health and well‐being in both generations. These experiences were linked to both positive and negative changes in parenting behaviour and parent–child relationships, which could be moderated by intersecting identities such as the parent's generational status for immigration to the United Kingdom. Social cohesion, safe spaces and education programmes were highlighted for future intervention. Conclusions: Findings corroborate existing literature, while further emphasising a broader bidirectional picture, requiring a family system and intersectional approach to understanding the mental health impact of racism in families. Avenues for future research are discussed to support development of equitable intervention and support strategies to prevent racism and support those affected.