Among this study’s limitations, the most notable is the focus on cohorts of European ancestry. This focus was required to maximize sample size and statistical power by combining summary statistics across GENOA, PGC-SUD, MVP and PH GWAS through application of the gSEM GWAS method. This approach allowed us to more than double the number of cases used in the EA-focused MVP-SAGE-YP analyses that yielded genome-wide significance for rs1799971 (n = 23,367 vs n = 10,544) by leveraging gSEM’s ability to model multiple correlated phenotypes and account for sample overlap. These gSEM analyses will be extended to African Americans when the needed ancestry-specific LDSC reference panel becomes available.
