Table 1.
Independent variants from each genome-wide significant locus in EA and AA smokers.
| Sample | Chr | Top SNP from region | Imputation Info (Quality) Score | MAF (%) | Effect Allele; Ref. Allele | Beta (SE); P-value | Gene location |
|---|---|---|---|---|---|---|---|
| EA females (n = 389) | 19 | rs56113850 | 0.92 in PNAT2 | 47.8 | C; T | 0.67 (0.07); 7.5e−22 | CYP2A6 (intron) |
| EA males (n = 541) | 19 | rs56113850 | 0.91 in PNAT2 | 44.9 | C; T | 0.75 (0.05); 1.2e−37 | CYP2A6 (intron) |
| AA females (n = 503) | 19 | rs11878604 | 0.98 in PNAT2, 0.93 in KIS3 | 22.8 | C; T |
− 0.71 (0.07); 6.6e−26c − 0.69 (0.11); 5.5e−10 in PNAT2 − 0.73 (0.09); 5.3e−15 in KIS3 |
CYP2A6 (16 kb 3′) |
| 19 | 19:41352257d | 0.90 in PNAT2, 0.92 in KIS3 | 31.9 | G; GT |
− 0.69 (0.07); 2.1e−25a,c − 0.68 (0.11); 2.9e−9 in PNAT2 − 0.69 (0.08); 2.8e−15 in KIS3 |
CYP2A6 (intron) | |
| 12 | rs12425845 | 1.0 in PNAT2, 0.99 in KIS3 | 8.4 | C; T |
0.64 (0.11); 5.0e−9c 0.73 (0.18); 7.1e−5 in PNAT2 0.59 (0.14); 2.9e−5 in KIS3 |
TMEM132C (1 Mb 5′) | |
| AA males (n = 352) | 19 | rs3865454 | 0.98 in PNAT2, 0.98 in KIS3 | 34.3 | G; T |
0.64 (0.07); 1.9e−19b 0.67 (0.09); 1.9e−11 in PNAT2 0.60 (0.11); 1.5e−7 in KIS3 |
CYP2A6 (7 kb 3′) |
| 6 | rs9379805 | 1.0 in PNAT2, 0.99 in KIS3 | 33.6 | A; T |
− 0.44 (0.08); 4.8e−9b − 0.34 (0.10); 8.3e−4 in PNAT2 − 0.58 (0.12); 1.6e−6 in KIS3 |
SLC17A2 (8 kb 5′) | |
| 16 | rs77368288 | 0.81 in PNAT2, 0.73 in KIS3 | 6.5 | C;T |
− 0.89 (0.16); 3.5e−8b − 0.96 (0.18); 4.6e−7 in PNAT2 − 0.65 (0.34); 5.4e−2 in KIS3 |
ZNF469 (92 kb 5′) |
Novel loci associated with the nicotine metabolite ratio (rank-transformed for analysis) were found in AA females and AA males and are indicated in italics.
EA European American, AA African American, Chr chromosome, info info (i.e. quality) score from imputation, MAF minor allele frequency, SE standard error.
Conditional analysis was used to determine the number of independent signals for each chromosome containing genome-wide significant variants.
aAfter conditioning on rs11878604, the beta (SE) for 19:41352257 was − 0.45 (0.08), and the P-value was 8.3e−9.
bBeta, SE, and P-value is reported for the meta-analyzed PNAT2 and KIS3 AA males.
cBeta, SE, and P-value is reported for the meta-analyzed PNAT2 and KIS3 AA females.
dNo rsID is available for this variant in dbSNP.