Variants in the CHRNA5-CHRNA3-CHRNB4 locus , including rs16969968 , a nonsynonymous variant in CHRNA5 , are genomewide association study-significantly associated with CO ( = 2.66 ; 95 % confidence interval [ CI ] , 1.74-3 .58 ; P = 1.65 10 ( -8 ) ) , and this association remains strong after adjusting for smoking behavior ( = 2.18 ; 95 % CI , 1.32-3 .04 ; P = 7.47 10 ( -7 ) ) .