Background: Offspring of parents with a history of depressive and anxiety disorders are at a higher risk of developing one themselves. Beyond direct inheritance, parental genes may also impact offspring outcomes through the environment in a “genetic nurture” pathway. The scarcity of relevant data has limited studies in this area, resulting in an incomplete understanding of the impact of this indirect role of genes on the familial transmission of depression and anxiety.
Methods: We investigated genetic nurture effects in 15,231-17,186 Dutch adults with at least one genotyped parent from Lifelines, a large general population cohort. We computed polygenic scores for transmitted (PGST) and non-transmitted (PGSNT) parental haplotypes using genome-wide association studies for depression. Using mixed-effect regression models, we analyzed PGST and PGSNT associations with offspring outcomes, ranging from narrow (depressive and anxiety disorders according to diagnostic criteria) to broader definitions (depressive and anxiety symptoms, neuroticism, and negative affect), measured at multiple assessment waves.
Results: Our findings demonstrate a pattern of significant associations between PGST and offspring outcomes, consistent with direct genetic transmission (PGST β=0.09—0.40, p<.001). PGSNT effects were approaching null across all outcomes, with some exceptions in specific assessment waves.
Conclusions: The lack of robust associations for PGSNT across outcomes suggests a minimal role of genetic nurture in depressive and anxiety disorders, symptoms and related traits through parental genetic liability for depression. Therefore, the familial transmission of depression and anxiety seems primarily driven by direct genetic inheritance.