Through the aggregation of genome-wide, genotypic data, we present molecular evidence for a substantial polygenic component to the risk of alcoholism. Although accounting for only a modest amount of variation in AD risk (R2 values less than 3%; Fig. 1), our polymarker scores are nonetheless significantly associated to AD in both EA and AA target samples, even for putative risk alleles with GWAS P-values as lax as 0.55 ≤ p < 0.60 (Fig. 2a), underscoring the statistical power issues faced by genome-wide studies of similarly complex, polygenic traits. When populations were mismatched between the discovery and target samples for the scoring routines, the resulting scores became poor predictors of alcoholism, suggesting that the genetic liabilities stem from patterns of allelic architecture that are predominantly population-specific, a finding that is consistent with the various novel genetic associations and linkage signals reported in ethnic studies (Gelernter & Kranzler 2009).
