Conditional analyses identified five independent associations within three previously reported loci and all five replicated (Table 3). At the 19q13 (RAB4B) locus, there were three variants in or near CYP2A6 associated with CPD independently of the established variant (rs7937) and each other: rs8102683 (conditional P = 4.53 × 10−16), rs28399442 (conditional P = 2.63 × 10−12) and rs3865453 (conditional P = 4.96 × 10−10) and rs28399442 was a low-frequency variant. The same SNVs also showed evidence of independent effects with pack-years, albeit with larger P-values (P < 5 × 10−6; Supp. Table 5). At the TEX41/PABPC1P2 locus, rs11694518 (conditional P = 3.43 × 10−7) was associated with smoking initiation independently of the established variant (rs10427255). At 15q25, rs938682 (P = 7.78 × 10−21) was associated with CPD independently of the established variant (rs1051730) and (in agreement with a previous report [49]) is an eQTL for CHRNA5 in brain putamen basal ganglia tissues in GTEx.
