Reviewer #2 (Public review): Heterogeneous associations of polygenic indices of 35 traits with mortality: a register-linked population-based follow-up study

This important study reports convincing evidence of associations between 35 polygenic indices (PGIs) for social, behavioural, and psychological traits, as well as other health conditions (e.g., BMI) and all-cause mortality, based on data from Finnish population-based surveys and a twin cohort linked to administrative registers.PGIs for education, depression, alcohol use, smoking, BMI, and self-rated health showed the strongest associations with all-cause mortality, in the order of ~10% increment in risk per PGI standard deviation.Effect sizes from twin-difference analyses tended to be slightly larger than those from population cohorts, a pattern opposite that generally observed when testing PGI associations with their target phenotypes, and supporting the robustness of findings to confounding by population stratification.