Table 2. Detailed results for the most interesting signals on 19q13.2.
First four rows represent the independent signals in the ranking order from the meta-analysis of conditional analyses. Last five rows represent known CYP2A6 alleles present in our data. Distribution of NMR and rank transformed NMR among the different genotype groups of these nine SNPs in the YFS sample are presented in S6 Fig.
| FinnTwin | Young Finns Study | FINRISK2007 | MAF | GWAS meta-analysis | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Location with respect to CYP2A6 | MAF | GWAS beta 1 (SD), p-value | % of variance explained | MAF | GWAS beta 1 (SD), p-value | % of variance explained | MAF | GWAS beta 1 (SD), p-value | % of variance explained | FINRISK 2 | EUR 3 | p-value | beta (coded allele) | beta (minor allele) | Estimated change in NMR 4 | |
| rs56113850 | C>T in intron 4 | 0.46 | -0.61 (0.07), p = 2.78E-17 | 14.4% | 0.45 | -0.70 (0.05), p = 4.56E-45 | 22.8% | 0.45 | -0.60 (0.07), p = 8.76E-19 | 17.0% | 0.44 | 0.41 | 5.77E-86 | -0.65 | -0.65 | -0.15 |
| rs113288603 5 | C>T in intron 1 | 0.15 | -0.01 (0.10), p = 0.89 | <0.01% | 0.15 | 0.07 (0.08), p = 0.34 | 0.14% | 0.15 | -0.03 (0.10), p = 0.78 | 0.04% | 0.15 | 0.09 | 0.663 | 0.02 | -0.02 | -0.005 |
| esv2663194 | del of exons 1–2 | 0.03 | 0.78 (0.23), p = 8.71E-04 | 3.12% | 0.04 | 1.18 (0.14), p = 4.14E-16 | 7.95% | 0.03 | 1.12 (0.24), p = 5.16E-06 | 4.72% | 0.03 | 0.02 | 3.34E-23 | 1.08 | -1.08 | -0.25 |
| rs12461964 6 | G>A in intron 1 | 0.48 | -0.53 (0.07), p = 9.35E-15 | N/A 7 | 0.44 | -0.63 (0.05), p = 2.25E-36 | N/A 7 | 0.45 | -0.63 (0.06), p = 4.79E-22 | 19.7% | 0.45 | 0.51 | 3.66E-76 | -0.61 | -0.61 | -0.14 |
| CYP2A6*2 8 | L160H | <0.01 | N/A 9 | 0.30% | 0.02 | 1.45 (0.21), p = 7.62E-12 | 6.12% | 0.02 | 0.81 (0.33), p = 0.01 | 1.46% | 0.01 | 0.03 | 8.64E-13 | 1.27 | -1.27 | -0.29 |
| CYP2A6*9 10 | promoter (-48T>G) | 0.14 | 0.45 (0.10), p = 1.06E-05 | 4.05% | 0.12 | 0.64 (0.08), p = 1.74E-14 | 6.98% | 0.13 | 0.81 (0.11), p = 1.72E-13 | 12.22% | 0.11 | 0.07 | 1.54E-30 | 0.63 | -0.63 | -0.14 |
| CYP2A6*14 11 | S29N | 0.02 | 0.21 (0.24), p = 0.39 | 0.28% | 0.02 | 0.33 (0.22), p = 0.14 | 0.19% | 0.01 | -0.11 (0.31), p = 0.73 | 0.02% | 0.01 | 0.04 | 0.191 | 0.19 | -0.19 | -0.04 |
| CYP2A6*18 12 | Y392F | 0.02 | -1.22 (0.30), p = 4.71E-05 | 2.93% | 0.02 | -0.84 (0.19), p = 1.39E-05 | 2.70% | <0.01 | N/A 9 | <0.01% | 0.02 | 0.02 | 5.24E-09 | -0.95 | -0.95 | -0.22 |
| CYP2A6*21 13 | K476R | 0.02 | 0.92 (0.23), p = 7.83E-05 | 2.63% | 0.03 | 0.66 (0.15), p = 1.39E-05 | 2.65% | 0.02 | 0.79 (0.28), p = 5.25E-03 | 1.90% | 0.02 | 0.01 | 1.39E-10 | 0.75 | -0.75 | -0.17 |
MAF, minor allele frequency; GWAS, genome-wide association study; SD, standard deviation; EUR, 1000Genomes reference panel of individuals of European descent; N/A, not available;
1 beta reported for the coded allele;
2 MAF calculated among 19857 FINRISK individuals;
3 MAF reported for the EUR population at the Ensembl database;
4 change in NMR is estimated by multiplying SD of NMR (SD = 0.23 in the combined meta-analysis sample) by the effect size of the minor allele;
5 rs113288603 showed no association in the GWAS but was identified as an independent signal in analyses conditioned on the top-SNP (rs56113850);
6 identified as an independent SNP only in the FINRISK2007 GWAS sample;
7 rs12461964 was not an independent signal in FinnTwin or YFS, thus variance explained was not estimated;
8 rs1801272;
9 not included in the GWAS due to MAF<0.01;
10 rs28399433;
11 rs28399435;
12 rs1809810;
13 rs6413474.