Table 1.
Results of Genomewide Association (Stage 1) and Replication (Stage 2) Analyses.*
| SNP | Chromosome | Location | Gene | Risk Allele |
Genomewide Association Analysis |
Replication Analysis: U.S. Cohort |
Replication Analysis: Canadian Cohort |
Replication Analysis: Both Cohorts (N = 526 Patients, N = 1206 Controls) |
Combined Analysis (N = 1031 Patients, N = 2713 Controls) |
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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Risk-Allele Frequency |
EIGENSTRAT P Value |
PLINK P Value |
Odds Ratio (95% Cl) |
Risk-Allele Frequency |
PLINK P Value |
Risk-Allele Frequency |
PLINK P Value |
Bonferroni- Corrected P Value |
P Value | Odds Ratio (95% Cl) |
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| kb | patients (N = 505) | controls (N=1507) | patients (N = 410) | controls (N = 310) | patients (N = 116) | controls (N = 896) | ||||||||||||
| HLA region | ||||||||||||||||||
| rs2856683 | 6p21.3 | 32763196 | HLA – DQB1 | C | 0.360 | 0.222 | 1.34×10−14 | 8.58×10−17 | 1.99 (1.69–2.34) |
0.334 | 0.228 | 1.44×10−5 | 0.298 | 0.224 | 1.30×10−2 | 3.18×10−5 | 1.78×10−19 | 1.75 (1.55–1.98) |
| rs9275312 | 6p21.3 | 32773706 | HLA – DQB1 | G | 0.227 | 0.128 | 1.99×10−11 | 3.84×10−13 | 2.01 (1.66–2.42) |
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| rs9275390 | 6p21.3 | 32777134 | HLA – DQB1 | G | 0.373 | 0.246 | 5.73×10−11 | 1.13×10−13 | 1.81 (1.55–2.11) |
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| rs7775228 | 6p21.3 | 32766057 | HLA – DQB1 | G | 0.207 | 0.122 | 1.90×10−10 | 1.70×10−10 | 1.87 (1.54–2.27) |
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| rs2395148 | 6p21.3 | 32429532 | C6orf10 | A | 0.055 | 0.019 | 1.50×10−9 | 5.62×10−10 | 3.24 (2.20–4.77) |
0.065 | 0.026 | 8.19×10−4 | 0.068 | 0.025 | 2.77×10−4 | 8.94×10−5 | 3.62×10−14 | 2.87 (2.16–3.82) |
| rs9277535 | 6p21.3 | 33162839 | HLA – DPB1 | G | 0.326 | 0.236 | 7.26×10−9 | 8.28×10−9 | 1.60 (1.36–1.87) |
0.318 | 0.248 | 3.85×10−3 | 0.331 | 0.250 | 7.83×10−3 | 2.32×10−3 | 3.92×10−11 | 1.50 (1.33–1.70) |
| rs3806156 | 6p21.3 | 32481676 | BTNL2 | A | 0.457 | 0.354 | 1.31×10−8 | 1.27×10−9 | 1.58 (1.37–1.84) |
0.428 | 0.361 | 0.01 | 0.42 | 0.360 | 0.07 | 0.07 | 1.11×10−9 | 1.42 (1.27–1.58) |
| rs9357152 | 6p21.3 | 32772938 | HLA – DQB1 | A | 0.826 | 0.741 | 3.88×10−8 | 7.25×10−8 | 1.65 (1.37–1.97) |
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| rs3135363 | 6p21.3 | 32497626 | BTNL2 | A | 0.784 | 0.718 | 4.46× 10−8 | 3.72×10−7 | 1.56 (1.30–1.85) |
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| rs9277565 | 6p21.3 | 33164875 | HLA – DPB1 | A | 0.276 | 0.198 | 5.94×10−8 | 8.32×10−8 | 1.58 (1.34–1.87) |
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| rs2281389 | 6p21.3 | 33167774 | HLA – DPB1 | G | 0.236 | 0.168 | 1.58×10−7 | 2.38×10−7 | 1.59 (1.33–1.90) |
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| rs660895 | 6p21.3 | 32685358 | HLA – DRB1 | G | 0.277 | 0.195 | 3.41×10−7 | 4.68×10−8 | 1.60 (1.35–1.90) |
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| rs9501626 | 6p21.3 | 32508322 | HLA – DRA | A | 0.173 | 0.110 | 4.43×10−7 | 6.83×10−7 | 1.68 (1.37–2.07) |
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| Non-HLA regions | ||||||||||||||||||
| rs6441286 | 3q25.33–q26 | 161211572 | IL12A | G | 0.497 | 0.390 | 1.20×10−8 | 3.25×10−8 | 1.51 (1.30–1.75) |
0.488 | 0.371 | 1.11×10−5 | 0.471 | 0.395 | 2.55×10−2 | 6.80×10−5 | 2.42×10−14 | 1.54 (1.38–1.72) |
| rs3790567 | 1p31.2 | 67594965 | IL12RB2 | A | 0.341 | 0.240 | 4.51×10−8 | 8.60×10−8 | 1.54 (1.32–1.81) |
0.311 | 0.241 | 5.19×10−3 | 0.340 | 0.246 | 1.72×10−3 | 0.005 | 2.76×10−11 | 1.51 (1.33–1.70) |
| rs574808 | 3q25.33–q26 | 161215677 | IL12A | T | 0.678 | 0.574 | 3.81×10−7 | 5.34×10−7 | 1.47 (1.27–1.72) |
0.668 | 0.564 | 6.97×10−5 | 0.677 | 0.588 | 9.26×10−3 | 2.78×10−5 | 1.88×10−13 | 1.54 (1.37–1.73) |
| rs6838639 | 4q27 | 123118615 | TRPC3 | G | 0.804 | 0.729 | 1.36×10−6 | 3.45×10−7 | 1.59 (1.33–1.92) |
0.764 | 0.780 | 0.48 | 0.727 | 0.735 | 0.80 | 1.00 | 2.35×10−3 | 1.23 (1.08–1.40) |
| rs3790565 | 1p31.2 | 67583944 | IL12RB2 | C | 0.258 | 0.183 | 2.50×10−6 | 1.41×10−6 | 1.53 (1.29–1.82) |
0.232 | 0.195 | 0.10 | 0.269 | 0.184 | 1.91×10−3 | 0.05 | 1.24×10−8 | 1.46 (1.28–1.67) |
| rs9964104 | 18q21 | 50751695 | CCDC68 | A | 0.687 | 0.606 | 8.37×10−6 | 2.77×10−5 | 1.39 (1.19–1.61) |
0.642 | 0.643 | 0.97 | 0.639 | 0.626 | 0.71 | 1.00 | 2.13×10−4 | 1.25 (1.11–1.40) |
| rs3124607 | 9q34.3 | 138534660 | NOTCH1 | G | 0.730 | 0.665 | 9.85×10−6 | 6.45×10−6 | 1.45 (1.24–1.70) |
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| rs16833239 | 2q32 | 191648505 | STAT4 | G | 0.962 | 0.921 | 1.55×10−5 | 2.60×10−5 | 2.13 (1.47–3.03) |
0.934 | 0.924 | 0.48 | 0.933 | 0.922 | 0.54 | 1.00 | 4.67×10−5 | 1.65 (1.30–2.10) |
| rs10222962 | 4p15 | 32036553 | PCDH7 | G | 0.111 | 0.070 | 1.55×10−5 | 1.67×10−5 | 1.70 (1.33–2.18) |
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| rs2211312 | 13q33.3 | 107203928 | FAM155A | A | 0.925 | 0.878 | 1.78×10−5 | 5.08×10−5 | 1.75 (1.33–2.33) |
0.879 | 0.887 | 0.63 | 0.865 | 0.878 | 0.59 | 1.00 | 0.61 | 1.05 (0.88–1.24) |
| rs907092 | 17q21 | 35175785 | IKZF3 | A | 0.522 | 0.449 | 2.05×10−5 | 7.04×10−6 | 1.40 (1.21–1.62) |
0.536 | 0.487 | 0.07 | 0.492 | 0.456 | 0.18 | 0.24 | 7.61×10−6 | 1.29 (1.15–1.44) |
| rs9303277 | 17q21 | 35229995 | IKZF3 | A | 0.571 | 0.495 | 2.75×10−5 | 3.95×10−5 | 1.41 (1.22–1.66) |
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| rs4679904 | 3q26.1 | 161823590 | ARF7 | G | 0.798 | 0.719 | 2.79×10−5 | 5.38×10−6 | 1.52 (1.27–1.79) |
0.767 | 0.710 | 0.02 | 0.748 | 0.730 | 0.55 | 0.51 | 1.13×10−6 | 1.38 (1.21–1.57) |
| rs2305480 | 17q12 | 35315722 | GSDMB | A | 0.509 | 0.438 | 3.66×10−5 | 1.41×10−5 | 1.38 (1.19–1.60) |
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| rs6140113 | 20p13 | 691770 | C20orf54 | G | 0.891 | 0.835 | 3.81×10−5 | 3.75×10−5 | 1.61 (1.30–2.04) |
0.849 | 0.831 | 0.36 | 0.765 | 0.813 | 0.05 | 1.00 | 0.34 | 1.08 (0.93–1.25) |
| rs10488631 | 7q32.1 | 128381419 | IRF5 – TNPO3 | G | 0.168 | 0.117 | 4.57×10−5 | 2.14×10−5 | 1.55 (1.26–1.90) |
0.167 | 0.113 | 4.72×10−3 | 0.130 | 0.090 | 0.14 | 0.05 | 1.52×10−7 | 1.52 (1.30–1.78) |
| rs6748358 | 2q33 | 204465150 | CTLA4 | C | 0.574 | 0.497 | 4.91×10−5 | 1.41×10−5 | 1.39 (1.19–1.62) |
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*
The single-nucleotide polymorphisms (SNPs) are listed in order of decreasing significance as indicated by the EIGENSTRAT P values; only those with P values of less than 5.0×10−7 in the HLA region and less than 5.0×10−5 in non-HLA regions are shown. The EIGENSTRAT and PLINK P values are for the comparison of allele frequency between patients and controls. For the joint replication analysis (stages 2a and 2b), P values were calculated with a Cochran–Mantel–Haenszel method of combining allele-frequency counts, and the Bonferroni correction was applied. For the combined analysis (stages 1 and 2), P values and odds ratios were calculated with the use of the Cochran–Mantel–Haenszel method of combining allele frequency counts.