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Chunk #17 — Results — Primary GWAS Analysis

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Genome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci.
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To verify our results in an independent sample, we used summary association data from the AD GWAS conducted by the Psychiatric Genomics Consortium (PGC) (38). Although to date this is the largest AD GWAS, its effective sample size (39) is much smaller than the one used in our analysis (PGC = 31,819; MVP = 143,965) so there is low statistical power to replicate our findings. Nevertheless, considering our six GWS results in trans-ancestry meta-analysis, we observed genome-wide significant replication of the chromosome 4 ADH1B*rs1229984 association (p=2.18×10−11), a nominal replication of chromosome 10 rs1577857 (p=2.44×10−3) and direction replication (i.e., the loci showed the same effect direction in both MaxAlc and AD) for all loci (Supplementary Table 4). We estimate that the probability to observe a direction replication of all six MVP-identified loci in PGC AD GWAS by chance is 1.7% (Supplementary Figure 6). Leveraging the polygenic architecture of the complex traits investigated, in the EUR sample, MaxAlc in MVP showed rg=0.87 with AD in the PGC cohort (p=4.78×10−9) by LDSC. For additional replication, we investigated UK Biobank data regarding nine traits