Gender differences in the association of polygenic risk and divergent depression trajectories from mid to late life: a national longitudinal study.

Our research fills a critical gap in the depression literature by utilizing a life course perspective to examine gender-gene interactions in association with depression trajectories over time. Using data from the Health and Retirement Study, we estimated multi-level negative binomial and logistic mixed models to analyze gender-specific trajectories of depressive symptoms (CESD-8) and potential clinical depression risk from middle to late adulthood in relation to gender-by-polygenic-risk (PRS) interactions. We found increasingly greater female-male gaps in the CESD-8 scale and a higher probability of clinical depression risk with increasing polygenic risk scores. Furthermore, females' higher genetic vulnerabilities to depressive conditions than males vary from ages 51 to 90 years, (e.g. 0.28 higher CESD-8 scale for females at ages 76-85 years than for similar-aged males; higher 3.44% probability of depression risk for females at ages 81-85 compared to similar-aged males) (e.g. about 2.40% higher probability of depression risk for females at ages 61-70 years than for similar-aged males) . This study contributes to new knowledge of how gender-by-polygenic-risk interactions are associated with depression trajectories across the life course.