Direct and indirect genetic pathways between parental neuroticism and offspring emotional problems across development: evidence from 7 cohorts across 5 European nations

Abstract

Disentangling direct and indirect genetic pathways underlying the intergenerational transmission of emotional problems could guide preventative strategies and further the understanding of the role of parental mental health in children's outcomes. This study aimed to estimate the extent to which genetic pathways that are direct (via child genotype) and indirect (e.g., via parental phenotype) explain the well-established association between parent and child emotional problems. We leveraged data from seven European cohort studies with a combined population of Ntrios=15,475. Polygenic scores were calculated for parental and offspring neuroticism, as it represents a dispositional trait underlying emotional problems. Emotional problems in offspring were measured using validated scales across various developmental stages from early childhood to adulthood. We used neuroticism polygenic scores within a structural equation modelling framework to distinguish between direct genetic pathways from parental genotype to offspring outcome (acting through offspring genotype), and indirect genetic pathways (acting through parental phenotype and associated environment). Standard errors for direct genetic, indirect genetic and total effects were bootstrapped and meta-analyses pooled effect estimates at three developmental stages (childhood: 3-4 years, adolescence: 11-13 years, adulthood: 18+ years). We found evidence suggesting an indirect genetic pathway between mothers and child emotional problems during early childhood (pooled estimate, mean difference in child emotional problems score per 1SD increase in maternal PGS for neuroticism=0.04, 95% CI: 0.01, 0.07). This association attenuated over child development, while direct genetic pathways strengthened. High attrition rates, measurement error and low variance explained by polygenic scores may have altered precision of the estimates, influencing the interpretation of the results. However, we provide the first multi-cohort study to provide evidence for an indirect genetic pathway from maternal neuroticism to early child emotional problems. This suggests that there are likely processes other than direct genetic pathways involved in the intergenerational transmission of emotional problems, highlighting the importance of timely support to prevent and reduce emotional issues in mothers as a preventative strategy for emotional difficulties.