Three SNPs in CHRNA5 (rs6495306, rs680244 and rs621849), in complete LD (r2 = 0.99), had a significant total effect (p = 0.03, FDR q = 0.023) and direct effects (p = 0.04, FDR q = 0.034), but the indirect effect through nicotine dependence was not significant. The gene discussed is CHRNA5; the disease is nicotine dependence.