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Chunk #21 — Discussion

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Hemizygous Deletion on Chromosome 3p26.1 Is Associated with Heavy Smoking among African American Subjects in the COPDGene Study.
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There are several genome-wide studies of SNP markers where smoking behaviors (including pack-years, nicotine dependence, etc.) have been used as outcome phenotypes. Several have achieved genome-wide significance among European Americans, but fewer among African Americans. In a recent meta-analysis of four smoking behavior phenotypes, David et al. [33] identified one SNP in chr 15q25.1 achieving genome-wide significance in a combined sample of 15,547 African American subjects from 13 studies with the phenotype cigarettes per day. This region of chr15q25.1 has shown strong and consistent evidence of association with nicotine dependence, smoking intensity and lung cancer risk in samples of European ancestry. These authors suggest this one SNP achieving genome-wide significance may define a single common haplotype exerting some effect on smoking behaviors. Among the second-tier hits identified in this meta-analysis were some novel genes, but none could account for much of the variance in quantitative measures of smoking behavior. In a candidate gene approach, Saccone et al. [34] confirmed a well-recognized association between a non-synonymous, functional SNP (rs16969968) in chr 15q25 and nicotine dependence in both European Americans and African