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Chunk #33 — DISCUSSION

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Genome-wide association study of alcohol dependence implicates a region on chromosome 11.
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yes

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Several SNPs nominated as candidates in earlier GWAS studies replicated in ours. Johnson et al. (Johnson et al., 2006) reported 51 regions, containing 181 SNPs, that provided the strongest evidence for association in a GWAS of alcohol dependence using pooled samples of 120 cases and 160 controls drawn from the COGA study (we do not know the overlap with the present study). Among the 68 of those SNPs for which we had data, 4 provided evidence of replication (p<0.02; Table 3). CPE encodes carboxypeptidase E, present in the central nervous system (Lynch et al., 1990), which catalyzes an important step in the processing of peptide hormones and neurotransmitters (Hook et al., 2008). A pair of closely linked SNPs in DNASE2B, encoding deoxyribonuclease II beta, provided evidence for replication, and other SNPs in that region provided further support. SLC10A2, which encodes a sodium/bile acid cotransporter, also replicated; expression of SLC10A2 is regulated in part by retinol (Neimark et al., 2004). Three other SNPs replicated when the subgroup with early-onset alcoholism was analyzed: rs35164 just downstream of CDH11 (a type II classical