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Chunk #33 — Discussion

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Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking.
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There are several limitations to this study. First, given the involvement of many groups across several countries and use of data collected for other purposes, methods for assessments were not consistent across all studies. The phrasing of questions differed across sites, and although an attempt was made to harmonize the phenotypes it would have been ideal to use the same tools and questions. Second, some groups did not have both AOI and AOS data, so direct comparison of results is incomplete because power to detect an association differs. Third, the exact same SNPs were not available for all groups, so we relied on the use of proxy SNPs based on the current HapMap data. It is possible that some of the SNPs used as proxies are not as well correlated with the target SNP signal as we believe, but given the large datasets now available, this is unlikely for most of the targets.