Table 2. Genome-wide significant differentially-methylated CpG sites of current compared to never smokers.
| Discovery panel (F4) | Replication panel (F3) | Meta-analysis | Methylation ß-value as median (first quartile - third quartile) | ||||||||||
| Discovery panel (F4) | Replication panel (F3) | ||||||||||||
| CpG | Chr | Gene | Median ß-value methylation difference in % | p-value | Explained variance in % | Median ß-value methylation difference in % | p-value | Explained variance in % | p-value | Never smokers | Current smokers | Never smokers | Current smokers |
| cg04885881 | 1 | xa | –7.41 | 1.35E-28 | 9.57 | –6.71 | 6.62E-13 | 9.83 | 7.19E-40 | 0.3115 (0.25–0.39) | 0.2374 (0.18–0.31) | 0.2899 (0.24–0.36) | 0.2228 (0.17–0.29) |
| cg15542713 | 1 | HIVEP3 | 9.52 | 2.54E-08 | 2.03 | 9.95 | 3.65E-13 | 9.51 | 3.56E-18 | 0.4002 (0.31–0.50) | 0.4954 (0.38–0.60) | 0.3784 (0.30–0.46) | 0.4779 (0.40–0.57) |
| cg25189904 | 1 | GNG12 | –8.19 | 1.71E-39 | 14.27 | –7.40 | 4.13E-15 | 11.42 | 9.11E-53 | 0.2740 (0.23–0.33) | 0.1921 (0.16–0.24) | 0.2856 (0.24–0.33) | 0.2116 (0.17–0.26) |
| cg12876356 | 1 | GFI1 | –8.48 | 2.92E-17 | 5.46 | –22.63 | 6.18E-18 | 13.59 | 2.47E-32 | 0.5475 (0.49–0.62) | 0.4627 (0.37–0.55) | 0.7010 (0.56–0.80) | 0.4746 (0.33–0.60) |
| cg09935388 | 1 | GFI1 | –15.31 | 3.27E-24 | 7.39 | –16.47 | 3.98E-26 | 18.93 | 1.26E-46 | 0.5765 (0.49–0.70) | 0.4234 (0.32–0.54) | 0.4757 (0.40–0.54) | 0.3110 (0.24–0.39) |
| cg27241845 | 2 | xa | –8.74 | 2.79E-35 | 10.96 | –8.36 | 2.07E-19 | 13.78 | 6.03E-53 | 0.4617 (0.41–0.52) | 0.3743 (0.31–0.42) | 0.4457 (0.41–0.49) | 0.3621 (0.31–0.43) |
| cg21566642 | 2 | ALPPL2b | –16.70 | 6.90E-138 | 36.24 | –15.58 | 8.82E-41 | 27.13 | 7.86E-175 | 0.5658 (0.51–0.61) | 0.3988 (0.35–0.45) | 0.5511 (0.50–0.59) | 0.3953 (0.31–0.44) |
| cg01940273 | 2 | ALPPL2b | –7.89 | 9.28E-114 | 31.50 | –7.53 | 5.46E-43 | 28.33 | 1.92E-154 | 0.3437 (0.32–0.37) | 0.2648 (0.24–0.29) | 0.2941 (0.27–0.31) | 0.2189 (0.20–0.25) |
| cg15693572 | 3 | xa | 10.87 | 3.84E-14 | 4.50 | 6.90 | 1.74E-06 | 4.60 | 3.69E-19 | 0.2942 (0.22–0.41) | 0.4029 (0.29–0.53) | 0.3159 (0.23–0.40) | 0.3850 (0.29–0.50) |
| cg23480021 | 3 | xa | 18.63 | 2.67E-22 | 8.74 | 15.77 | 1.95E-10 | 8.09 | 3.63E-31 | 0.4259 (0.30–0.60) | 0.6122 (0.44–0.78) | 0.4266 (0.29–0.58) | 0.5844 (0.43–0.78) |
| cg03274391 | 3 | xa | 18.06 | 1.67E-25 | 8.79 | 11.93 | 3.74E-10 | 7.78 | 5.47E-34 | 0.3190 (0.23–0.47) | 0.4997 (0.34–0.70) | 0.2872 (0.21–0.41) | 0.4065 (0.29–0.55) |
| cg15417641 | 3 | CACNA1D | 7.92 | 1.25E-16 | 4.90 | 5.28 | 1.90E-06 | 4.61 | 1.65E-21 | 0.6818 (0.58–0.76) | 0.7610 (0.68–0.83) | 0.6019 (0.52–0.68) | 0.6546 (0.60–0.73) |
| cg21188533 | 3 | CACNA1D | 10.18 | 1.12E-10 | 3.10 | 5.56 | 4.38E-05 | 3.42 | 2.33E-14 | 0.5724 (0.45–0.69) | 0.6742 (0.55–0.76) | 0.5309 (0.41–0.63) | 0.5865 (0.50–0.70) |
| cg03991871 | 5 | AHRR | –5.73 | 4.84E-41 | 12.72 | –7.88 | 1.23E-23 | 17.61 | 8.03E-63 | 0.9469 (0.92–0.96) | 0.8896 (0.80–0.93) | 0.9175 (0.89–0.94) | 0.8387 (0.69–0.89) |
| cg05575921 | 5 | AHRR | –24.40 | 2.54E-182 | 41.02 | –23.29 | 1.81E-64 | 39.69 | 8.70E-244 | 0.8841 (0.86–0.90) | 0.6401 (0.60–0.73) | 0.9028 (0.88–0.92) | 0.6699 (0.58–0.77) |
| cg26703534 | 5 | AHRR | –6.17 | 2.14E-38 | 10.90 | –5.77 | 7.83E-25 | 17.21 | 3.66E-61 | 0.6269 (0.60–0.65) | 0.5652 (0.52–0.60) | 0.6180 (0.60–0.63) | 0.5603 (0.53–0.60) |
| cg25648203 | 5 | AHRR | –7.96 | 4.73E-47 | 12.98 | –7.55 | 2.03E-23 | 16.96 | 1.01E-68 | 0.8642 (0.83–0.89) | 0.7846 (0.72–0.84) | 0.8473 (0.81–0.87) | 0.7719 (0.71–0.82) |
| cg21161138 | 5 | AHRR | –10.45 | 8.58E-81 | 21.63 | –10.60 | 1.19E-40 | 28.49 | 1.49E-119 | 0.6998 (0.67–0.73) | 0.5954 (0.53–0.65) | 0.7304 (0.70–0.75) | 0.6244 (0.57–0.68) |
| cg06126421 | 6 | xa | –17.05 | 1.72E-75 | 23.60 | –17.89 | 3.73E-36 | 24.58 | 8.42E-110 | 0.7724 (0.70–0.82) | 0.6019 (0.48–0.69) | 0.6919 (0.63–0.74) | 0.5131 (0.42–0.61) |
| cg14753356 | 6 | xa | –5.37 | 8.14E-24 | 8.58 | –6.41 | 2.98E-23 | 17.61 | 5.90E-44 | 0.2383 (0.20–0.28) | 0.1846 (0.15–0.22) | 0.2451 (0.20–0.28) | 0.1810 (0.15–0.22) |
| cg00931843 | 6 | TIAM2 | 6.37 | 1.69E-10 | 2.98 | 5.66 | 1.09E-07 | 5.73 | 1.37E-16 | 0.2963 (0.23–0.39) | 0.3600 (0.27–0.47) | 0.3293 (0.25–0.42) | 0.3859 (0.29–0.46) |
| cg22132788 | 7 | MYO1G | 6.68 | 1.99E-34 | 11.04 | 5.02 | 8.44E-18 | 13.68 | 1.54E-50 | 0.8599 (0.81–0.90) | 0.9267 (0.88–0.95) | 0.8727 (0.83–0.90) | 0.9229 (0.88–0.95) |
| cg12803068 | 7 | MYO1G | 14.96 | 7.08E-30 | 10.34 | 15.12 | 1.04E-15 | 12.29 | 6.33E-44 | 0.7382 (0.60–0.85) | 0.8878 (0.77–0.94) | 0.7014 (0.60–0.81) | 0.8527 (0.71–0.92) |
| cg11207515 | 7 | CNTNAP2 | 8.28 | 2.53E-10 | 3.44 | 5.29 | 2.16E-07 | 5.30 | 3.77E-16 | 0.2725 (0.21–0.35) | 0.3552 (0.27–0.44) | 0.2166 (0.17–0.27) | 0.2695 (0.21–0.33) |
| cg25305703 | 8 | xa | –6.05 | 2.09E-08 | 2.97 | –6.17 | 6.16E-09 | 6.16 | 2.75E-15 | 0.7103 (0.65–0.76) | 0.6498 (0.58–0.73) | 0.6679 (0.62–0.71) | 0.6062 (0.54–0.67) |
| cg26361535 | 8 | ZC3H3 | –5.54 | 4.14E-09 | 2.83 | –6.35 | 4.39E-07 | 4.90 | 1.35E-14 | 0.7593 (0.70–0.81) | 0.7040 (0.63–0.77) | 0.7442 (0.69–0.79) | 0.6807 (0.64–0.75) |
| cg21611682 | 11 | LRP5 | –5.24 | 1.09E-18 | 6.50 | –5.38 | 3.16E-20 | 14.13 | 9.90E-36 | 0.5276 (0.50–0.56) | 0.4752 (0.43–0.52) | 0.4844 (0.46–0.51) | 0.4306 (0.40–0.47) |
| cg23126342 | 13 | PCDH9 | 9.11 | 7.16E-14 | 4.38 | 7.56 | 2.73E-08 | 6.20 | 1.23E-20 | 0.5136 (0.43–0.60) | 0.6047 (0.52–0.67) | 0.4865 (0.39–0.57) | 0.5621 (0.46–0.64) |
| cg01208318 | 14 | xa | –7.74 | 2.54E-12 | 4.15 | –6.20 | 1.20E-05 | 3.59 | 1.57E-16 | 0.2836 (0.20–0.37) | 0.2063 (0.16–0.28) | 0.2246 (0.15–0.30) | 0.1626 (0.12–0.23) |
| cg19572487 | 17 | RARA | –10.02 | 9.37E-40 | 14.02 | –7.81 | 7.56E-15 | 11.92 | 9.85E-53 | 0.4477 (0.40–0.51) | 0.3475 (0.30–0.43) | 0.4502 (0.40–0.51) | 0.3722 (0.31–0.44) |
| cg00835193 | 19 | LINGO3 | –8.23 | 2.44E-08 | 2.26 | –11.66 | 4.40E-07 | 5.01 | 9.20E-14 | 0.8822 (0.75–0.93) | 0.7999 (0.61–0.92) | 0.8938 (0.77–0.94) | 0.7772 (0.59–0.91) |
| cg03636183 | 19 | F2RL3 | –14.74 | 2.42E-80 | 22.45 | –17.63 | 1.65E-39 | 26.94 | 5.58E-118 | 0.4930 (0.45–0.54) | 0.3456 (0.28–0.43) | 0.5152 (0.47–0.56) | 0.3390 (0.28–0.43) |
Displayed are the results of the linear model calculated with M-value adjusted for age, sex, BMI, alcohol and white blood cell count (p-value and explained variance), as well as the median ß-value methylation difference between current and never smokers for the discovery panel (F4) with genome-wide significance (p-value ≤1E-07) for all CpG sites with a DNA methylation difference of >5% in F4 and F3, the corresponding results of the same CpG sites for the replication panel F3 for comparison (significance level ≤5E-05) and the corresponding p-value gained by meta-analysis of F4 and F3, sorted by chromosome and mapinfo (Genome build 37). a According to UCSC Genome Browser no annotated transcripts are associated with these CpG sites; b According to UCSC Genome Browser no annotated transcripts are associated with these CpG sites, but SNPs within the same region (shore of a CpG Island) have a predicted function on the ALPPL2 gene, which is located several kb apart from this CpG island.