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Chunk #25 — Discussion

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Association of CHRN genes with "dizziness" to tobacco.
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This study supports a previous report, in a separate sample, of an association between the CHRNB3 gene (Zeiger et al., 2008) and early subjective response to tobacco, specifically “dizziness.” The “dizziness” item was selected as the only subjective effect for this analysis based on its high contribution to two genetically-derived prinicipal components phenotypes associated with CHRNB3 in our previous study (Figure 2 in (Zeiger et al., 2008)) and to minimize false-positive findings that may occur with multiple testing of several phenotypes. After correcting for all 17 SNPs tested in the gene, the overall empirical p-value for the gene reached significance at p=0.021 (Table 3). Within the gene, multiple SNPs in the putative promoter region of CHRNB3 reached nominal significance, while none of the SNPs in other regions showed any evidence for association with “dizziness” (Table 2). In addition, evidence for a connection between two other CHRN genes (CHRNA4 and CHRNA10) emerged from our secondary analysis of all SNPs that had been genotyped. The CHRNA4 gene (rs3787140) reached a similar level of significance as CHRNB3 for the top individual SNP empirical