We applied PRS to the COGA Prospective Study EA dataset, controlling for sex, ancestry (using the first four principal components as indicated by the scree plot) (Figure S1), family history, and relatedness. We used the frailty model to capture relatedness for the COGA data; this is the most widely used method to handle correlated survival data (50). Specifically, the frailty model puts a random effect term in the Cox regression formula such that the members of the same family will share the same random effect.
