Table 2.
Eight Genome-Wide Signals for Asthma-COPD Overlap
| rsID | Chr:Pos (Effect/Noneffect Allele) | Nearest Gene | Location | EAF | Stage 1 (UK Biobank; Case Subjects, 8,068; Control Subjects, 40,360) |
Stage 2 (12 Independent Studies; Case Subjects, 4,301; Control Subjects, 48,609)a |
Joint Analysis of Stage 1 and Stage 2 |
|||
|---|---|---|---|---|---|---|---|---|---|---|
| OR (95% CI) | P Value | OR (95% CI) | P Value | OR (95% CI) | P Value | |||||
| rs80101740 | 5:98471135 (C/A) | LOC100289230 | Intergenic | 0.015 | 1.44 (1.24-1.68)a | 1.87 × 10–6a | 1.37 (1.10-1.71) | 5.49 × 10–3 | 1.42 (1.25-1.61) | 3.72 × 10–8 |
| rs35570272 | 3:33047662 (T/G) | GLB1 | Intronic | 0.398 | 1.11 (1.07-1.15) | 1.06 × 10–7 | 1.08 (1.02-1.14) | 4.67 × 10–3 | 1.10 (1.06-1.13) | 2.44 × 10–9 |
| rs16903574 | 5:14610309 (G/C) | FAM105A | Exonic | 0.077 | 1.23 (1.15-1.32) | 4.47 × 10–9 | 1.13 (1.03-1.25) | 9.96 × 10–3 | 1.20 (1.13-1.27) | 3.8 × 10–10 |
| rs2584662 | 17:47470487 (C/A) | PHB | Intergenic | 0.42 | 0.90 (0.86-0.94) | 3.20 × 10–8 | 0.95 (0.90-1.00) | 5.89 × 10–2 | 0.92 (0.89-0.95) | 2.21 × 10–8 |
| rs1837253 | 5:110401872 (C/T) | TSLP | Intergenic | 0.739 | 1.22 (1.17-1.27) | 4.22 × 10–21 | 1.06 (1.00-1.12) | 4.44 × 10–2 | 1.16 (1.12-1.20) | 1.53 × 10–18 |
| rs6787279 | 3:57163751 (C/T) | IL17RD | Intronic | 0.169 | 0.88 (0.84-0.92) | 2.69 × 10–7 | 0.91 (0.85-0.97) | 6.51 × 10–3 | 0.89 (0.86-0.93) | 7.87 × 10–9 |
| rs9273410 | 6:32627250 (A/C) | HLA-DQB1 | UTR3 | 0.445 | 1.24 (1.19-1.29) | 4.37 × 10–27 | 1.11 (1.05-1.18) | 6.42 × 10–4 | 1.20 (1.16-1.24) | 9.19 × 10–28 |
| rs3749833 | 5:131799626 (C/T) | C5orf56 | ncRNA intronic | 0.263 | 1.16 (1.11-1.21) | 3.10 × 10–12 | 1.06 (1.00-1.12) | 4.21 × 10–2 | 1.12 (1.09-1.16) | 9.37 × 10–12 |
Variants were annotated with nearest gene and type of region, using ANNOVAR software (and genome build hg19). OR, 95% CI, and P value were all calculated by score testing. The Firth test for rs80101740 gave OR, 1.40 (95% CI, 1.22-1.60) and P = 1.56 × 10–6. Chr:Pos = chromosome:position; EAF = effect allele frequency; ncRNA = noncoding RNA; rsID = reference SNP (single-nucleotide polymorphism) ID number; UTR3 = 3' (three prime) untranslated region.
Stage 2 studies: CHS (Cardiovascular Health Study), COPDGene (Genetic Epidemiology of COPD), deCODE, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints), EPIC-Norfolk (European Prospective Investigation of Cancer in Norfolk), FHS (Framingham Heart Study), Generation Scotland, GenKOLS (Genetics of Chronic Obstructive Lung Disease Study), Trøndelag Health Study (HUNT), Lovelace Smokers' Cohort, Rotterdam Study, SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study).