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Chunk #22 — RESULTS — ANYDEP and QUANTDEP — Genetic Analysis

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Association of substance dependence phenotypes in the COGA sample.
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The second genome-wide significant finding was observed with QUANTDEP and a genotyped SNP rs2567261 on chromosome 18 in the gene ARHGAP28 (Rho GTPase activating protein 28) (p=3.8×10−8). Due to the low minor allele frequency for this SNP (MAF=0.08), AA and AG genotypes were combined. Although individuals dependent on opioids and cocaine had higher QUANTDEP scores on average (main effect of substance p<0.0001; Figure 3B), there was no substance*genotype effect (p=0.74) confirming that QUANTDEP exhibited the same pattern by genotype across the 4 substances. Analysis of the imputed SNPs in this region further supported the association (Figure 4B). There was no evidence of replication in SAGE for QUANTDEP (p=0.29). Corresponding SAGE results for the SNPs are provided in Table 2.