Recent meta-analyses have suggested that our more focused study design has paid off, with our ascertained sample that included a narrow age range and specific smoking behavior requirements increased power to detect genetic variation compared to a more heterogeneous GWAS. Two of the top genetic findings −rs16969968 in CHRNA5 and rs6474412 in CHRNB3—showed significance levels of 5.57 × 10−72 with a sample size of N = 73,853 (TAG, 2010) and 1.4 × 10−8 with a sample size of N = 84,956 (Thorgeirsson et al., 2010). In our COGEND sample of 2,062 subjects of European descent, we have a significance level of 4 × 10−7 for the CHRNA5 variant and 1.37 × 10−3 for the variant in CHRNB3 (Saccone et al., 2010a; Saccone et al., 2010b), representing a 3 and 10 fold increase in the power to detect genetic variation compared to a more heterogeneous GWAS. These comparisons demonstrate the amplified power of a study design through the systematic ascertainment, targeted age range, and phenotypic contrast of lifetime light smokers versus current heavy smokers.
