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Chunk #39 — Discussion

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Genome-wide association analyses suggested a novel mechanism for smoking behavior regulated by IL15.
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From these nine SNPs, we choose four SNPs (rs4956302, rs17354547, rs1402812 and rs4956396) to replicate our association findings in an AA family-based cohort containing 1,251 subjects, including 412 males and 839 females. We selected rs4956302 due to the fact that it achieved the highest significance among all the SNPs tested genome-wide in our GWAS cohort. We also selected rs17354547 because it is highly conserved across multiple species. Another two SNPs (rs1402812 and rs4956396) were randomly chosen since all seven of the remaining significant SNPs are in high LD and had similar p values. Interestingly, a male-specific association with multiple ND phenotypes was observed for the SNP rs17354547; in male subjects of our AA replication cohort SNP rs17354547 achieved p values of 0.031, 0.0046 and 0.019 for association with SQ, HSI and FTND, respectively (Table 3). Furthermore, in male subjects from our replication sample, a haplotype formed by the SNPs rs17354547, rs1402812 and rs4956396 was also associated with SQ, HSI and FTND, with p values of 0.039, 0.0093 and 0.0093, respectively. The replication results support our GWAS findings for an association between smoking behavior and these SNPs located upstream from the IL15 gene.