Prior genome-wide studies of CPD did not identify the CHRNA4 region at genome-wide significance, likely owing to differences in phenotype definition and lower SNP coverages.3, 4, 5, 6, 7, 8, 9, 38, 54, 55 Regarding phenotype definition, we found that our top SNP rs2273500 was most significantly associated with time to first cigarette in the morning (P=2.3 × 10−8, Supplementary Table 7). In contrast, for the missense CHRNA5 SNP rs16969968 that has reproducible associations with both nicotine dependence (Supplementary Table 1) and CPD,5, 6, 7 the lowest P-value, by far, was observed for CPD (P=9.4 × 10−24, Supplementary Table 8). rs16969968 has previously also shown strong association with cotinine levels, which reflect recent nicotine intake.56, 57
