The genetic correlation (rg) between MVP phase1 AUD and PGC AD was 0.965 (se = 0.15, p = 1.21 × 10−10) [3]. The rg between the entire MVP (meta-analysis of phase1 and phase2) and PGC was 0.98 (se = 0.11, p = 1.99 × 10−19), justifying the meta-analysis of AUD across the three datasets (neffective = 179,185). We detected 24 risk variants in 23 loci in this intermediary meta-analysis (Figure 2a, Supplementary Table 1). The rg between UKB AUDIT-P and AUD (MVP+PGC) was 0.71 (se = 0.05, p = 8.15 × 10−52), and the polygenic risk score (PRS) of AUD was associated with AUDIT-P in UKB (best p-value threshold PTbest = 0.001, R2 = 0.25%, p = 3.28 × 10−41, Supplementary Table 2, Supplementary Figure 1), justifying the proxy-phenotype meta-analysis of problematic alcohol use (PAU) across all four datasets. (AUD and AUDIT-P, though highly correlated genetically, are not identical traits). The total sample size was 435,563 in the discovery analysis (neffective = 300,789).
