The first goal of this meta-analysis project was to test whether distinct loci in the CHRNA5-CHRNA3-CHRNB4 gene cluster demonstrate independent effects on smoking behavior (heavy (CPD>20) versus light (CPD≤10) smoking). We selected loci for study based on prior statistical and/or functional evidence for involvement. The second goal was to test whether similar patterns of association are seen across these loci in the smoking-related diseases of lung cancer and COPD. This meta-analysis marks the first large-scale effort to line up association results for these related traits – smoking, lung cancer, and COPD – using a uniform analysis protocol. Our results contribute important new insights about genetic risk for these traits. In particular, we demonstrate strong evidence that smoking behavior is influenced by multiple distinct loci in this region, including two loci that are associated with relevant biological effects in functional studies.
