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Chunk #12 — COMMENT

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Association of variants in MANEA with cocaine-related behaviors.
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We observed that several polymorphic markers in the MANEA gene region are associated with cocaine-related traits in 2 EA and 2 AA populations, which were ascertained and analyzed in different ways. The strongest evidence was obtained for CIP with markers in the MANEA coding and promoter regions, spanning a distance of approximately 33.6 kb (ie, between rs9320497 and rs9387522). Haplotype analysis in the replication data sets helped confirm that the rs9387522 A allele is associated with increased risk of CIP in all 4 populations. This SNP is only 348 bp from rs1133503, the marker in the low-density genome scan that showed an association with CIP in the EA and AA family-based samples,24 which prompted this investigation. Our comprehensive analysis of MANEA SNPs and haplotypes in 4 independent data sets bolsters our initial association finding and indicates that the biologically relevant variant is most likely located in the 3′ UTR.