Table 2.
Gene variants with genome-wide significance for moderate-to-severe asthma, by chromosome
| Position | Variant | Locus | Non-coded | Coded | Minor allele | MAF | rsid.ukb (proxy r2) |
Stage 1 cohort |
Stage 2 cohort |
Meta-analyses of stage 1 and 2 |
||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OR (95% CI) | p value | OR (95% CI) | p value | OR (95% CI) | p value | |||||||||
| Novel | ||||||||||||||
| 4 | 123 055 701 | rs560026225 | KIAA1109 | G | GATT | GATT | 23·60% | rs72687036 (0·66) | 1·15 (1·09–1·21) | 4·62 × 10−7 | 1·09 (1·04–1·15) | 7·50 × 10−4 | 1·12 (1·08–1·16) | 3·06 × 10−9 |
| 10 | 8 115 362 | rs10905284 | GATA3 | C | A | C | 42·94% | rs10905284 | 0·87 (0·84–0·91) | 2·01 × 10−9 | 0·94 (0·90–0·98) | 2·25 × 10−3 | 0·90 (0·88–0·93) | 1·76 × 10−10 |
| 11 | 1 136 478 | rs11603634 | MUC5AC | A | G | A | 49·64% | rs11603634 | 1·13 (1·08–1·18) | 2·30 × 10−8 | 1·05 (1·01–1·10) | 1·82 × 10−2 | 1·09 (1·06–1·12) | 2·32 × 10−8 |
| Previous | ||||||||||||||
| 1 | 167 427 247 | rs7523907 | CD247 | C | T | C | 45·92% | rs7523907 | 1·14 (1·10–1·20) | 1·64 × 10−9 | 1·05 (1·00–1·10) | 2·11 × 10−2 | 1·10 (1·06–1·13) | 4·82 × 10−9 |
| 2 | 102 949 161 | rs12479210 | IL1RL1 | C | T | T | 38·73% | rs12479210 | 1·20 (1·15–1·26) | 4·77 × 10−16 | 1·19 (1·14–1·24) | 4·82 × 10−15 | 1·19 (1·16–1·23) | 1·57 × 10−29 |
| 2 | 242 698 640 | rs34290285 | D2HGDH | G | A | A | 25·74% | rs34290285 | 0·82 (0·78–0·87) | 1·41 × 10−14 | 0·85 (0·81–0·89) | 1·16 × 10−10 | 0·84 (0·81–0·87) | 2·24 × 10−23 |
| 5 | 110 401 872 | rs1837253 | TSLP | T | C | T | 25·84% | rs1837253 | 1·24 (1·18–1·30) | 8·49 × 10−18 | 1·14 (1·08–1·20) | 1·75 × 10−7 | 1·19 (1·15–1·23) | 1·95 × 1−22 |
| 5 | 110 467 499 | rs1438673 | WDR36 | C | T | T | 49·22% | rs1438673 | 0·87 (0·84–0·91) | 2·35 × 10−9 | 0·91 (0·87–0·95) | 1·33 × 10−5 | 0·89 (0·86–0·92) | 3·29 × 10−13 |
| 5 | 131 799 626 | rs3749833 | C5orf56 | T | C | C | 26·08% | rs3749833 | 1·17 (1·12–1·23) | 1·14 × 10−10 | 1·11 (1·06–1·16) | 2·69 × 10−5 | 1·14 (1·10–1·18) | 5·60 × 10−14 |
| 5 | 131 887 986 | rs1986009 | RAD50 | C | A | A | 18·71% | rs1986009 | 1·18 (1·11–1·24) | 1·39 × 10−8 | 1·16 (1·10–1·23) | 4·11 × 10−8 | 1·17 (1·13–1·22) | 2·43 × 10−15 |
| 6 | 32 581 739 | rs776111176 | HLA-DQA1 | A | AAT | A | 14·85% | rs3997872 (0·82) | 0·82 (0·79–0·88) | 1·81 × 10−8 | 0·85 (0·81–0·90) | 2·62 × 10−9 | 0·84 (0·81–0·88) | 2·61 × 10−16 |
| 6 | 32 627 250 | rs9273410 | HLA-DQB1 | C | A | C | 44·70% | rs9273410 | 1·26 (1·20–1·32) | 1·07 × 10−24 | 1·16 (1·11–1·21) | 2·14 × 10−10 | 1·21 (1·17–1·25) | 5·62 × 10−32 |
| 6 | 91 001 332 | rs367983479 | BACH2 | CA | C | C | 38·50% | rs1504215 (0·89) | 0·88 (0·85–0·93) | 7·12 × 10−8 | 0·92 (0·88–0·96) | 1·12 × 10−4 | 0·90 (0·87–0·93) | 6·30 × 10−11 |
| 8 | 81 266 924 | rs71266076 | MIR5708 | C | CT | C | 36·93% | rs13274067 (0·97) | 0·87 (0·83–0·91) | 4·21 × 10−9 | 0·91 (0·87–0·95) | 1·57 × 10−5 | 0·89 (0·86–0·92) | 6·53 × 10−13 |
| 9 | 6 208 030 | rs144829310 | IL33 | G | T | T | 16·40% | rs144829310 | 1·23 (1·16–1·30) | 3·68 × 10−12 | 1·19 (1·13–1·26) | 1·12 × 10−9 | 1·21 (1·16–1·26) | 2·29 × 10−20 |
| 10 | 9 043 404 | rs61840192 | LOC101928272 | G | A | A | 42·70% | rs1775555 (0·98) | 0·85 (0·81–0·88) | 8·42 × 10−14 | 0·86 (0·82–0·89) | 1·14 × 10−12 | 0·85 (0·83–0·88) | 8·33 × 10−25 |
| 11 | 76 293 726 | rs7936312 | C11orf30 | G | T | T | 47·42% | rs7936312 | 1·14 (1·10–1·19) | 1·09 × 10−9 | 1·19 (1·14–1·24) | 3·38 × 10−16 | 1·17 (1·13–1·20) | 6·18 × 10−24 |
| 12 | 56 449 875 | rs7305461 | RPS26 | A | C | A | 44·61% | rs1131017 (0·98) | 0·88 (0·84–0·92) | 1·65 × 10−8 | 0·94 (0·90–0·98) | 2·51 × 10−3 | 0·91 (0·88–0·94) | 1·01 × 10−9 |
| 12 | 57 497 005 | rs703816 | STAT6 | T | C | C | 43·41% | rs703816 | 1·16 (1·11–1·21) | 1·18 × 10−11 | 1·08 (1·03–1·13) | 4·31 × 10−4 | 1·12 (1·09–1·15) | 3·69 × 10−13 |
| 15 | 61 068 704 | rs10519068 | RORA | G | A | A | 12·75% | rs10519068 | 0·85 (0·79–0·90) | 4·81 × 10−7 | 0·85 (0·79–0·90) | 5·76 × 10−7 | 0·85 (0·81–0·89) | 1·84 × 10−12 |
| 15 | 67 441 750 | rs72743461 | SMAD3 | C | A | A | 23·60% | rs72743461 | 1·18 (1·12–1·24) | 1·03 × 10−10 | 1·11 (1·06–1·17) | 2·35 × 10−5 | 1·14 (1·11–1·19) | 4·52 × 10−14 |
| 16 | 11 230 703 | rs7203459 | CLEC16A | T | C | C | 24·56% | rs7203459 | 0·81 (0·77–0·86) | 7·83 × 10−16 | 0·90 (0·85–0·94) | 2·33 × 10−5 | 0·86 (0·83–0·89) | 4·37 × 10−18 |
| 17 | 37 910 368 | rs2941522 | IKZF3 | C | T | T | 48·29% | rs2941522 | 1·13 1·08–1·18) | 1·46 × 10−8 | 1·10 (1·05–1·14) | 1·97 × 10−5 | 1·11 (1·08–1·15) | 2·32 × 10−12 |
| 17 | 47 439 302 | rs112502960 | ZNF652 | G | A | A | 35·92% | rs12952581 (0·98) | 1·14 (1·09–1·20) | 6·05 × 10−9 | 1·08 (1·04–1·13) | 3·92 × 10−4 | 1·11 (1·08–1·15) | 4·12 × 10−11 |
Results from case-control analyses for the variants that were significant in stage 1 and stage 2, showing the same direction of effect and reached genome-wide significance in the meta-analysis of stages 1 and 2. MAF corresponds to that from the stage 1 study and we give the OR per copy of the coded allele. rs1438673 was conditioned on rs1837253, rs1986009 was conditioned on rs3749833, and rs776111176 was conditioned on rs9273410. Stage 1 p values have genomic control applied.rs61816761 (FLG) was excluded and not included here following sensitivity analyses. r2 between stage 2 and stage 1 variants are given if a proxy was used in stage 2. MAF=minor allele frequency. rsid.ukb=rs number of variant used in stage 2 analyses using UK Biobank imputed data. OR=odds ratio.