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Chunk #20 — Results — Replication of association in SAGE and OZALC studies

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A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53.
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Seventy-two SNPs that associated with SC (with corrected p<10−4) in the COGA families were tested in SAGE. Based on a prior hypothesis (our initial results from GWAS) for each SNP regarding the direction of effect, we found 5/72 SNPs showing nominal association with the same direction of effect for SC (0.007≤p≤0.05). However, none of these SNPs is significant after correcting for multiple testing. We then tested the replication of the 18 SNPs in C15orf53 that showed suggestive evidence of association with SC in COGA sample (inflation corrected p=1.0×10−5). Using imputed data, 8 of these 18 SNPs showed nominal association with SC in SAGE sample (p≤0.03) (Table S3). These 18 SNPs all lie within a single LD bin (r2=0.8, D′≥0.9), so the data shown in Table S3 reflects a single statistical test.