Table 2. Loci with Genomewide Significance for Asthma and Tests of Heterogeneity across Studies*.
| Chromosome | Location | Allele | Childhood Onset | Later Onset | Total Sample† | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gene† | Marker | Position‡ | Ref | Alt | Alt Fq | Odds Ratio (95% CI) | P Value, Random Effects | Odds Ratio (95% CI) | P Value, Random Effects | Odds Ratio (95% CI) | P Value, Random Effects | P Value, Heterogeneity | P Value, Fixed Effects | |
| Loci with genomewide significance — P random ≤7.2×10−8 | ||||||||||||||
|
| ||||||||||||||
| 2 | IL18R1 | rs3771166§ | 102352654 | G | A | 0.38 | 0.85 (0.81–0.90) | 1.1×10−8 | 0.94 (0.85–1.04) | 1.9×10−1 | 0.87 (0.83–0.91) | 3.4×10−9 | 1.8×10−1 | 3.5×10−12 |
|
| ||||||||||||||
| 6 | HLA-DQ | rs9273349 | 32733847 | T | C | 0.58 | 1.14 (1.08–1.22) | 1.9×10−5 | 1.26 (1.16–1.37) | 3.9×10−8 | 1.18 (1.13–1.24) | 7.0×10−14 | 5.0×10−1 | 7.0×10−14 |
|
| ||||||||||||||
| 9 | IL33 | rs1342326 | 6180076 | A | C | 0.16 | 1.27 (1.17–1.38) | 1.6×10−8 | 1.12 (0.99–1.26) | 6.8×10−2 | 1.20 (1.13–1.28) | 9.2×10−10 | 2.2×10−1 | 8.7×10−12 |
|
| ||||||||||||||
| 15 | SMAD3 | rs744910 | 65233839 | G | A | 0.51 | 0.89 (0.84–0.93) | 8.1×10−6 | 0.94 (0.87–1.0) | 1.4×10−1 | 0.89 (0.86–0.92) | 3.9×10−9 | 8.5×10−1 | 3.9×10−9 |
|
| ||||||||||||||
| 17 | GSDMB | rs2305480 | 35315722 | G | A | 0.45 | 0.76 (0.72–0.81) | 6.4×10−23 | 1.03 (0.94–1.13) | 4.9×10−1 | 0.85 (0.81–0.90) | 9.6×10−8 | 9.2×10−4 | — |
|
| ||||||||||||||
| 17 | GSDMA | rs3894194 | 35375519 | G | A | 0.45 | 1.26 (1.19–1.33) | 3.0×10−17 | 1.02 (0.94–1.11) | 6.0×10−1 | 1.17 (1.11–1.23) | 4.6×10−9 | 2.0×10−2 | — |
|
| ||||||||||||||
| 22 | IL2RB | rs2284033 | 35863980 | G | A | 0.44 | 0.92 (0.87–0.97) | 1.6×10−3 | 0.86 (0.80–0.94) | 4.2×10−4 | 0.89 (0.86–0.93) | 1.2×10−8 | 9.2×10−1 | 1.2×10−8 |
|
| ||||||||||||||
| Additional loci — P random ≤5×10−7 | ||||||||||||||
|
| ||||||||||||||
| 5 | SLC22A5 | rs2073643 | 131751187 | T | C | 0.55 | 0.89 (0.84–0.93) | 7.6×10−6 | 0.94 (0.87–1.0) | 1.5×10−1 | 0.90 (0.87–0.94) | 2.2×10−7 | 8.3×10−1 | 2.2×10−7 |
|
| ||||||||||||||
| 5 | IL13 | rs1295686 | 132023742 | T | C | 0.80 | 0.85 (0.79–0.90) | 3.3×10−7 | 0.94 (0.85–1.04) | 2.6×10−1 | 0.87 (0.83–0.92) | 1.4×10−7 | 3.3×10−1 | 1.4×10−8 |
|
| ||||||||||||||
| 15 | RORA | rs11071559 | 58857280 | C | T | 0.14 | 0.88 (0.81–0.95) | 1.0×10−3 | 0.78 (0.69–0.88) | 5.7×10−5 | 0.85 (0.80–0.90) | 1.1×10−7 | 8.4×10−1 | 1.1×10−7 |
Markers are identified according to their standard rs numbers. Only single-nucleotide polymorphisms (SNPs) with significant or independent effects (according to stepwise regression analysis) on the risk of asthma are shown. The total sample includes all case subjects and controls. A complete list of SNPs with genomewide significance is available in Table 2 in the Supplementary Appendix. P values are shown for tests of association under a random-effects model, tests of heterogeneity across studies with the use of Cochran’s Q test, and tests of association under a fixed-effects model when there was no significant evidence of heterogeneity. For the calculation of these odds ratios, alternate alleles (Alt) were designated as risk alleles. Alt Fq denotes alternative allele frequency, CI confidence interval, and Ref reference allele.
The nominal gene was taken from the Illumina SNP database.
Position is based on the number of base pairs from the start of the chromosome.
The rs3771166 SNP was imputed in the MRC Asthma and United Kingdom Control panel (MRCA-UKC) and in the Multicenter Asthma Genetics in Childhood Study (MAGICS) panel.