Genetic associations detected in GWAS can be due to direct genetic effects, but can also be confounded by population stratification, indirect genetic effects from e.g., parental environment, and assortative mating47,48. While reducing statistical power, sibling comparisons overcome these methodological challenges, because meiosis randomizes genotypes to siblings47,49. We therefore conducted within-family analyses of polygenic score associations in the sibling sub-samples of Add Health (N = 994 siblings from 492 families) and COGA (N = 1,353 siblings from 621 families), and a sibling sample from the UKB (N = 39,640), which were held-out from the discovery stage (Supplementary Information section 2.3.2).
