We hypothesized that additional low frequency and rare coding variants in CHRNA5 alter risk for nicotine dependence. To comprehensively assess the relationship between CHRNA5 coding variation and liability to nicotine dependence, we analyzed targeted sequence data from approximately 3000 nicotine dependent cases and non-dependent controls of European and African descent. Additionally, we used 12 studies with exome chip data to replicate associations of common and low frequency variants with smoking behaviors. Finally, we studied the variance explained in the development of nicotine dependence by the rare, low frequency, and common polymorphisms in CHRNA5.
