Table 2.
Genome-wide analysis | Replication analysis | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Allele frequencies (Cases/Controls) | Allele frequencies (Cases/Controls) | ||||||||||||||||
Chr | SNP | Position | Locus | Al | Scandinavia (332/262) |
Germany (383/2700) |
P-value* | OR (95% CI)* | Scandinavia (289/820) |
Central Europe (561/2063) |
United States (371/625) |
P -value† | OR (95% CI) † | BD P value |
Combined P -value |
Het P- Value |
SNP selection strategy |
1 | rs3748816 | 2,516,606 | TNFRSF14/MMEL1 | G/A | 0.29/0.34 | 0.28/0.33 | 6.5×10−4 | 0.79 (0.69–0.90) | 0.31/0.35 | 0.30/0.34 | 0.27/0.35 | 8.7×10−6 | 0.79 (0.71–0.88) | 0.45 | 2.1×10−8 | 0.92 | I |
4 | rs13132245 | 123,269,042 | KIAA1109/IL2/IL21 | G/A | 0.16/0.21 | 0.12/0.17 | 7.3×10−5 | 0.69 (0.57–0.83) | 0.13/0.18 | 0.12/0.14 | 0.12/0.15 | 3.0×10−4 | 0.77 (0.67–0.89) | 0.65 | 1.2×10−7 | 0.40 | II |
4 | rs13119723 | 123,437,763 | KIAA1109/IL2/IL21 | G/A | 0.13/0.18 | 0.09/0.14 | 4.1×10−5 | 0.65 (0.53–0.80) | 0.15/0.19 | 0.13/0.15 | 0.12/0.16 | 4.0×10−4 | 0.78 (0.68–0.90) | 0.87 | 9.9×10−8 | 0.32 | II |
9 | rs4077515 | 138,386,317 | CARD9 | T/C | 0.48/0.45 | 0.43/0.40 | 0.045 | 1.14 (1.00–1.31) | 0.49/0.45 | 0.47/0.42 | 0.45/0.42 | 5.3×10−4 | 1.18 (1.08–1.30) | 0.95 | 7.6×10−5 | 0.55 | I |
16 | rs2903692 | 11,146,284 | CLEC16A | A/G | 0.28/0.33 | 0.31/0.36 | 0.0014 | 0.80 (0.92–0.70) | 0.27/0.33 | 0.32/0.35 | 0.32/0.36 | 0.0012 | 0.85 (0.76–0.94) | 0.43 | 6.4×10−6 | 0.64 | I |
2 | rs13017599 | 61,017,835 | REL | A/G | 0.40/0.35 | 0.40/0.37 | 0.027 | 1.16 (1.32–1.02) | 0.40/0.36 | 0.42/0.38 | 0.38/0.37 | 0.0026 | 1.16 (1.05–1.28) | 0.42 | 1.9×10−4 | 0.88 | I |
21 | rs11203203 | 42,709,255 | UBASH3A | A/G | 0.39/0.35 | 0.42/0.37 | 0.0025 | 1.22 (1.39–1.07) | 0.39/0.34 | 0.39/0.36 | 0.40/0.36 | 0.0033 | 1.16 (1.05–1.28) | 0.68 | 2.9×10−5 | 0.60 | I |
19 | rs602662 | 53,898,797 | FUT2 | A/G | 0.56/0.50 | 0.53/0.46 | 7.7×10−5 | 1.30 (1.49–1.14) | 0.53/0.47 | 0.48/0.45 | 0.51/0.50 | 0.0034 | 1.15 (1.05–1.27) | 0.29 | 1.9×10−6 | 0.21 | II |
21 | rs9976767 | 42,709,459 | UBASH3A | G/A | 0.48/0.46 | 0.48/0.44 | 0.028 | 1.15 (1.02–1.30) | 0.45/0.43 | 0.47/0.44 | 0.49/0.43 | 0.0055 | 1.14 (1.04–1.26) | 0.44 | 4.0×10−4 | 0.99 | I |
19 | rs601338 | 53,898,486 | FUT2 | A/G | 0.50/0.44 | 0.47/0.40 | 4.5×10−5 | 1.33 (1.52–1.16) | 0.51/0.44 | 0.46/0.42 | 0.48/0.48 | 0.0061 | 1.14 (1.04–1.26) | 0.062 | 2.7×10−6 | 0.14 | II |
2 | rs11682163 | 3,727,421 | ALLC | C/T | 0.49/0.39 | 0.49/0.44 | 7.9×10−5 | 1.29 (1.47–1.14) | 0.50/0.45 | 0.49/0.44 | 0.43/0.45 | 0.010 | 1.13 (1.03–1.24) | 0.048 | 7.6×10−6 | 0.14 | II |
19 | rs281377 | 53,898,415 | FUT2 | T/C | 0.43/0.49 | 0.46/0.52 | 9.3×10−6 | 0.71 (0.61–0.83) | 0.39/0.47 | 0.47/0.49 | 0.44/0.44 | 0.011 | 0.88 (0.80–0.97) | 0.025 | 2.1×10−6 | 0.059 | II |
22 | rs5771069 | 48,777,607 | IL17REL | A/G | 0.48/0.54 | 0.49/0.53 | 0.0057 | 0.82 (0.95–0.72) | 0.45/0.49 | 0.47/0.50 | 0.48/0.50 | 0.028 | 0.90 (0.82–0.99) | 0.89 | 5.8×10−4 | 0.43 | I |
4 | rs11936230 | 123,236,205 | KIAA1109/IL2/IL21 | T/C | 0.38/0.30 | 0.41/0.35 | 1.9×10−5 | 1.33 (1.17–1.52) | 0.38/0.34 | 0.38/0.36 | 0.38/0.36 | 0.039 | 1.11 (1.01–1.22) | 0.79 | 1.9×10−5 | 0.040 | II |
12 | rs4149056 | 21,222,816 | SLCO1B1 | C/T | 0.13/0.17 | 0.16/0.17 | 0.044 | 0.84 (1.00–0.70) | 0.14/0.17 | 0.15/0.16 | 0.13/0.15 | 0.043 | 0.87 (0.76–1.00) | 0.60 | 0.0045 | 0.76 | I |
22 | rs4820599 | 23,320,213 | GGT1 | G/A | 0.29/0.24 | 0.31/0.28 | 0.035 | 1.16 (1.01–1.33) | 0.29/0.28 | 0.29/0.27 | 0.31/0.28 | 0.043 | 1.11 (1.00–1.23) | 0.77 | 0.0038 | 0.69 | I |
12 | rs3184504 | 110,368,991 | SH2B3 | T/C | 0.54/0.52 | 0.57/0.51 | 0.0016 | 1.23 (1.08–1.40) | 0.47/0.45 | 0.51/0.49 | 0.51/0.47 | 0.050 | 1.10 (1.00–1.21) | 0.67 | 4.6×10−4 | 0.21 | I |
Complete association results for SNPs reaching nominal significance with consistent effect sizes in the replication. For the genome-wide analysis, the allele frequencies were calculated based on allele dosages and are listed separately for the German and Scandinavian discovery panels. For the replication analysis, allele frequencies are given for all three panels making up the combined replication panel. The combined P-values for the genome-wide analysis and the replication analysis were generated using the METAL software [34]. The genomic positions refer to NCBI’s build 36. SNP selection strategies I and II indicate SNPs selected based on the two SNP selection strategies. The HLA association was confirmed for rs4143332 (Prepl=4.1×10−77, Pcomb=4.4×10−123) (not listed in the table).
Chr, chromosome; Al, alleles; OR, Odds Ratio; CI, Confidence Interval; BD, Breslow-Day; Het, heterogeneity
Odds ratios and P-values derived from logistic regressions of allele dosages including the six first principal components from the principal components analysis as covariates.
P-values generated by using the Cochrane-Mantel-Haenszel test