To examine the impact of these associated CHRN variants, we calculated Nagelkerke’s adjusted R2 from logistic regression of case-control status (Nagelkerke, 1991), comparing the base model with intercept, gender, and age to the model with selected SNPs added, in AAs and EAs separately. This quantity represents the proportion of trait variation explained by the SNPs, in the given sample; it is scaled so that an appropriate maximum of 1 is achieved in the case where the sample is 50% cases and 50% controls, and case-control status is predicted perfectly by the variables. We first calculated R2 for three SNPs (rs16969968, rs578776, and rs588765) on chromosome 15q25 that demonstrate association with nicotine dependence (Saccone et al., 2009b). We then added SNPs representing the regions highlighted by our current results: CHRND-CHRNG (rs1881492), CHRNA4 (rs2236196), CHRNB3-CHRNA6 (rs13277254), CHRNB1 (rs7210231), CHRNA7 (rs6494212), and CHRNA10 (rs2231532). Each of these regions contains at least one SNP with p ≤ 0.05 in the full COGEND sample (2-df association test), and for each region we chose the SNP with the lowest p-value.
