These results should be considered in the context of several limitations. First, the COGA sample is enriched with individuals with SUDs, and the results may not generalize to lower-risk samples. Second, the sibling comparison design assumes that siblings are reared together. Not all COGA participants were asked about their living arrangements while growing up, and so we could not test whether this assumption was met for all sibling groups. However, to address this concern, we restricted the analyses to the sibling groups where it was possible to determine that they grew up together, and to siblings who were born close together in time (and thus more likely to share aspects of their rearing environment compared to siblings born further apart). The pattern of effects remained significant and in the same direction in these sensitivity analyses, suggesting that the effects observed in our sibling comparisons of polygenic scores were not driven by differences in siblings’ rearing environments.
