The present study illustrates how sibling comparisons can improve our understanding of the shared genetic etiology underlying educational attainment and substance use problems. Consistent with previous findings that educational attainment has a negative genetic correlation with alcohol problems [11, 13], cannabis use disorder [14], and smoking [12], we found that individuals met fewer SUD criteria when they carried more alleles associated with educational attainment. We replicated these effects within a sibling comparisons design, where we found that individuals met fewer clinically significant substance use criteria when they carried more alleles associated with higher educational attainment than their siblings. Sibling comparisons are uniquely powerful because they control for unmeasured confounding factors shared by siblings that could otherwise explain the association between educational attainment polygenic scores and substance use disorder criteria: factors such as socioeconomic status, urban-rural residency, and parental education. Thus, our findings suggest that the association between educational attainment polygenic scores and SUDs is not completely explained by confounders that differ between families.
