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Chunk #22 — DISCUSSION

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Nominal association with CHRNA4 variants and nicotine dependence.
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In the current study we investigated the role of genetic variation in the genes that code for the α4 and β2 nAChR subunits in a quantitative measure of lifetime DSM-IV ND symptoms in two separate samples. Six and eight SNPs in each gene (CHRNA4 and CHRNB2, respectively) were examined in the CADD sample using methods that account for linkage disequilibrium between SNPs. Modest evidence for association with two SNPs was detected in CHRNA4. In CHRNA4, the minor alleles of rs1044394 and rs1044396 were associated with increased risk for ND symptoms (p=0.010 and 0.027, respectively). This association was strongest in the non-Hispanic EA portion of the sample, and although the number of informative families increased with the addition of the Hispanic population, this did not provide additional support for an association. However, when these SNPs were examined in the GADD sample, the associations did not replicate.