Second, our sibling comparison analyses demonstrated that polygenic scores were significant predictors of SUD criteria even within families. For outcomes like SUDs, which have considerable influences that vary among families, ruling out familial confounding is particularly important. In addition to significant sibling differences, we also found that between-family differences in EduYears-GPS predicted SUDs. This suggests that both the overall polygenic loading of one’s family and one’s relative polygenic loading within that family are important predictors of risk for SUDs. The associations between sibling differences in polygenic scores and SUDs were attenuated somewhat after controlling for sibling differences in phenotypic educational attainment. This attenuation may reflect the relative statistical power of polygenic scores compared to the phenotypes from which they are derived, as well the likelihood that some of the effect of sibling differences in educational attainment polygenic scores is likely to be mediated through sibling differences in educational persistence, as has been documented previously [26].
