Genetic nurture effects in depressive and anxiety disorders and symptoms, and in related traits.

There is an elevated risk of depression and anxiety in offspring of parents with a history of these disorders. Beyond direct transmission, 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 indirect impact of parental genes on the familial transmission of depression and anxiety. 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 (PGS-T) and non-transmitted (PGS-NT) parental haplotypes using genome-wide association studies for depression. Using mixed-effect regression models, we analyzed PGS-T and PGS-NT 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. Our results demonstrate a pattern of significant associations between PGS-T and offspring outcomes, consistent with direct genetic transmission (OR = 1.2-1.5; β = 0.09-0.20, p < 0.001). PGS-NT effects were approaching null across all outcomes, with some exceptions in specific assessment waves. The lack of robust associations for PGS-NT across outcomes suggests a minimal role of genetic nurture in depressive and anxiety disorders, symptoms, and related traits through parental genetic liability for depression. Though the possibility of indirect genetic effects through other genetic risk factors remains, our findings point to the genetic transmission of depression and anxiety primarily occurring via direct inheritance.