TABLE 2.
Fine-mapping of the MHC region harboring race/ethnicity-specific signals using sequenced data. We evaluated the joint effects of multiple variants on late-onset asthma with stepwise regression models. Conditional analyses of race/ethnicity-specific lead SNPs identified potential causal SNPs in the MHC region for all, White, and Black participants.
| All participants | ||||||
|---|---|---|---|---|---|---|
| Variants | Position | Gene | Alleles | Freq | OR (95% CI) a | p-value |
| rs9265901 | 6:31345615 | HLA-B | A|G | 1.01 (1.00, 1.03) | 0.05 | |
| rs59377618 | 6:32820360 | HLA-DOB | T|C | 1.02 (1.01, 1.04) | 4.42 × 10−3 | |
| 6:33097139 | 6:33097139 | HLA-DPA1 | G|A | 0.98 (0.97, 0.99) | 4.62 × 10−3 | |
| rs2894334 | 6:33330567 | SMIM40 | A|C | 0.99 (0.98, 0.99) | 0.01 | |
| rs5009448 | 6:29972711 | HLA-A | T|C | 1.01 (1.00, 1.02) | 0.02 | |
| rs7767589 | 6:30402196 | RPP21 | C|T | 1.07 (1.02, 1.13) | 7.00 × 10−3 | |
| rs73728546 | 6:31380112 | MICA | C|T | 1.05 (1.02, 1.09) | 5.24 × 10−3 | |
| rs4569 | 6:31670030 | LY6G5B | C|T | 0.98 (0.97, 0.99) | 3.21 × 10−3 | |
| 6:33061419 | 6:33061419 | HLA-DPB1 | C|T | 1.10 (1.05, 1.16) | 2.23 × 10−4 | |
| rs9268541 | 6:32416750 | BTNL2 | T|C | 1.03 (1.00, 1.05) | 0.02 | |
| rs62407970 | 6:32969217 | HLA-DMA | G|A | 1.03 (1.01, 1.05) | 6.89 × 10−3 | |
| White participants | ||||||
| rs55888430 | 6:32817365 | HLA-DOB | G|A | 1.03 (0.99, 1.07) | 0.06 | |
| rs5009448 | 6:29972711 | HLA-A | T|C | 1.02 (1.01, 1.03) | 1.65 × 10−3 | |
| rs116062523 | 6:31383028 | MICA | T|C | 1.08 (1.03, 1.14) | 3.64 × 10−3 | |
| rs7754362 | 6:33143251 | HCG24, COL11A2 | A|C | 0.98 (0.97, 0.99) | 2.95 × 10−4 | |
| 6:29800571 | 6:29800571 | A|C | 1.07 (1.01, 1.13) | 0.02 | ||
| 6:29816791 | 6:29816791 | A|T | 1.05 (1.00, 1.10) | 0.04 | ||
| 6:31932537 | 6:31932537 | CFB | T|C | 1.07 (1.04, 1.11) | 2.91 × 10−5 | |
| rs1632859 | 6:31002121 | MUC22 | G|A | 1.01 (1.00, 1.03) | 0.04 | |
| rs17208209 | 6:32227599 | NOTCH4 | G|A | 1.04 (1.00, 1.08) | 0.04 | |
| rs115337486 | 6:33387741 | KIFC1 | C|T | 1.04 (1.00, 1.08) | 0.04 | |
| Black participants | ||||||
| rs117953947 | 6:30244862 | TRIM26, HCG17 | G|A | 1.13 (0.98, 1.30) | 0.09 | |
| rs150891754 | 6:28608725 | ZBED9 | A|G | 1.27 (1.13, 1.44) | 1.20 × 10−4 | |
| rs17200414 | 6:31449359 | MICB | C|T | 1.21 (1.05, 1.38) | 7.90 × 10−3 | |
| rs200535118 | 6:31352792 | HLA-B | G|T | 1.19 (1.01, 1.40) | 0.04 | |
| rs62408569 | 6:29406052 | OR5V1, OR12D2 | C|T | 1.31 (1.13, 1.52) | 4.04 × 10−4 | |
| rs181714996 | 6:33331782 | SMIM40 | T|C | 1.19 (1.07, 1.32) | 1.05 × 10−3 | |
| rs115571466 | 6:32998090 | HLA-DOA | A|G | 1.20 (1.07, 1.35) | 1.71 × 10−3 | |
| rs4713423 | 6:31034524 | MUC22 | G|C | 1.04 (1.00, 1.08) | 0.03 | |
| rs17198965 | 6:31308446 | HLA-C | C|G | 1.08 (1.02, 1.16) | 0.01 | |
| rs73403122 | 6:32501344 | HLA-DRB5 | A|G | 1.21 (1.07, 1.36) | 1.92 × 10−3 | |
| rs17422797 | 6:32297751 | NOTCH4 | C|T | 1.26 (1.09, 1.44) | 1.38 × 10−3 | |
| rs79735834 | 6:29517075 | MAS1L | A|G | 1.08 (1.02, 1.15) | 0.01 | |
| rs187569734 | 6:31044172 | MUC22 | G|A | 1.28 (1.11, 1.48) | 6.82 × 10−4 | |
a
Odds ratios represent the association between lead SNPs (rs9265901, rs55888430, rs117953947) and late-onset asthma, adjusted for covariates and additional SNPs in forward stepwise regression analyses. We adjusted all regression models for age, sex, and four ancestries.
Note: A full list of the variants identified from conditional analyses is available in the Supplementary Table S4.