Top associations in exome discovery analyses and meta-analysis of COPD risk
| (A) SNPs with p<10–5 in either the pack-years adjusted or unadjusted discovery analyses | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Discovery pack-years adjusted analysis (2517 cases, 3889 controls) | Discovery unadjusted analysis (3226 cases, 4784 controls) | UK BiLEVE pack-years adjusted analysis (4231 cases, 8979 controls) | Meta-analysis of discovery and UK BiLEVE pack-year adjusted analyses | |||||||||||||||
| MAF (MAC) | Association result | MAF (MAC) | Association result | MAF (MAC) | Association result | Association result | ||||||||||||
| rs no. | CHR | Position | Coded allele | Gene | Cases | Controls | OR (95% CI) | p Value* | Cases | Controls | OR (95% CI) | p Value* | Cases | Controls | OR (95% CI) | p Value* | OR (95% CI) | p Value* |
| rs3813803 | 1 | 28282292 | C | SMPDL3B (non-synonymous) | 30.6% (1541) | 28.3% (2203) | 1.370 (1.207 to 1.554) | 2.41×10−6 | 30.3% (1956) | 28.5% (2722) | 1.288 (1.160 to 1.430) | 2.11×10−6 | 28.7% (2418) | 29.4% (5269) | 0.968 (0.911 to 1.029) | 0.298 | 1.033 (0.978 to 1.092) | 0.241 |
| rs17368582 | 11 | 102738075 | C | MMP12 (synonymous) | 11.1% (561) | 12.9% (1001) | 0.767 (0.642 to 0.915) | 3.22×10−3 | 11.1% (719) | 12.8% (1229) | 0.712 (0.615 to 0.824) | 5.01×10−6 | 12.0% (1015) | 12.2% (2198) | 0.982 (0.902 to 1.069) | 0.676 | 0.938 (0.868 to 1.013) | 0.101 |
| rs3827522 | 12 | 42853871 | A | PRICKLE1 (non-synonymous) | 0.2% (11) | 0.4% (27) | 0.184 (0.065 to 0.519) | 1.39×10−3 | 0.2% (14) | 0.5% (46) | 0.123 (0.057 to 0.266) | 1.03×10−7 | 0.3% (21) | 0.3% (45) | 0.907 (0.518 to 1.585) | 0.731 | 0.633 (0.386 to 1.039) | 0.071 |
| rs8034191 | 15 | 78806023 | C | near AGPHD1 (intergenic) | 38.0% (1912) | 32.7% (2546) | 1.374 (1.218 to 1.550) | 2.42×10−7 | 37.7% (2432) | 32.9% (3144) | 1.364 (1.234 to 1.507) | 1.18×10−9 | 39.2% (3315) | 35.2% (6320) | 1.156 (1.092 to 1.224) | 6.85×10−7 | 1.193 (1.133 to 1.257) | 2.79×10−11 |
| rs7269297 | 20 | 49576664 | G | MOCS3 (non-synonymous) | 0.7% (37) | 1.4% (110) | 0.251 (0.140 to 0.448) | 3.08×10−6 | 0.8% (54) | 1.5% (139) | 0.423 (0.262 to 0.680) | 3.98×10−4 | 1.2% (98) | 1.4% (252) | 0.742 (0.578 to 0.953) | 0.019 | 0.626 (0.497 to 0.789) | 7.27×10−5 |
| (B) SNPs with p<10–5 in the meta-analysis (only most statically significant SNP in each region shown) | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Discovery pack-years adjusted analysis (2517 cases, 3889 controls) | UK BiLEVE pack-years adjusted analysis (4231 cases, 8979 controls) | Meta-analysis of discovery and UK BiLEVE pack-year adjusted analyses | ||||||||||||
| MAF (MAC) | Association result | MAF (MAC) | Association result | Association result | ||||||||||
| rs no. | CHR | Position | Coded allele | Gene | Cases | Controls | OR (95% CI) | p Value* | Cases | Controls | OR (95% CI) | p Value* | OR (95% CI) | p Value* |
| rs1828591 | 4 | 145480780 | A | GYPA/HHIP (intergenic) | 35.6% (1794) | 39.1% (3042) | 0.9167 (0.814, 1.032) | 0.153 | 36.6% (3088) | 40.0% (771) | 0.867 (0.819, 0.918) | 9.88×10−7 | 0.876 (0.832, 0.922) | 5.75×10−7 |
| rs4896582 | 6 | 142703877 | A | GPR126 (intronic) | 29.3% (1473) | 31.7% (2468) | 0.8594 (0.757, 0.974) | 0.018 | 28.0% (2349) | 30.2% (5344) | 0.879 (0.826, 0.934) | 3.87×10−5 | 0.875 (0.827, 0.925) | 2.53×10−6 |
| rs140549288 | 10 | 91099466 | C | IFIT3 (exonic), LIPA (intronic) | 0.8% (38) | 0.6% (44) | 2.156 (1.046, 4.445) | 0.037 | 0.9% (79) | 0.6% (100) | 1.880 (1.378, 2.565) | 6.87×10−5 | 1.924 (1.441, 2.560) | 8.56×10−6 |
*p Values in bold significant at p<10−5 level.
BiLEVE, Biobank Lung Exome Variant Evaluation; MAC, minor allele count; MAF, minor allele frequency; SNPs, single nucleotide polymorphisms.