Maternal depression and the polygenic p factor: A family perspective on direct and indirect effects

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 modelling of trio polygenic p was used to distinguish direct and indirect genetic effects on mother’s 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 mother’s 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 modelling 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 and a negative interaction between child genes and time (b = -0.024, 95% CI [-0.045,0.004]), indicating the effect of time on depression differs as a function of child liability to psychiatric disorders. Our results support the generalizability of polygenic effects across mental health and highlight the importance of incorporating longitudinal data into our within-family analyses