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Chunk #23 — DISCUSSION

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Nicotinic acetylcholine receptor beta2 subunit gene implicated in a systems-based candidate gene study of smoking cessation.
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The present study has both strengths and limitations. Strengths include the prospective evaluation of abstinence in the setting of a placebo-controlled trial and collection of DNA samples from all participants, rather than retrospective DNA collection that may result in bias. With regards to the molecular genetic analysis, strengths include conservative SNP selection, robust genotyping, and extensive quality control. Because we performed our SNP selection on an early version of HapMap, we opted to use a high r2 cutoff (0.95) in selecting tagSNPs and including all singleton SNPs. This proved to be a prudent strategy as our set of SNPs captured on an average 85% of the existing common SNPs in the current version of HapMap. While this strategy resulted in a higher number of correlated SNPs within each gene, this did not have a detrimental impact on the analysis as we accounted for the correlation in our multiple testing procedures. Furthermore, a slight level of redundancy in SNP coverage allowed for a more stringent criteria for the removal of SNPs with low call rates, resulting in 97% of the analyzed