Table 3.
Top Results of the Genome-Wide Association Study for Subjects with Chronic Obstructive Pulmonary Disease with a Pulmonary Artery:Ascending Aorta Ratio Greater Than 1 versus Smokers with Normal Spirometry in the Cohorts of COPDGene Non-Hispanic Whites, COPDGene African Americans, and ECLIPSE Studies*
| Locus | Nearest Gene | SNP | Risk Allele | FRQ |
COPDGene NHW |
COPDGene AA |
ECLIPSE |
Overall |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EUR† | AA | OR (95% CI) | P Value | OR (95% CI) | P Value | OR (95% CI) | P Value | OR (95% CI) | P Value | I2 | Q | ||||
| 15q25.1 | CHRNA5 | rs17486278 | C | 0.37 | 0.29 | 1.43‡ (1.23–1.65) | 2.05 × 10−6 | 1.54‡ (1.24–1.91) | 9.26 × 10−5 | 1.22‡ (0.92–1.62) | 1.69 × 10−1 | 1.42 (1.27–1.59) | 6.93 × 10−10 | 0 | 0.43 |
| 15q25.1 | PSMA4 | rs58365910 | C | 0.38 | 0.26 | 1.43‡ (1.24–1.66) | 1.82 × 10−6 | 1.51‡ (1.20–1.88) | 3.55 × 10−4 | 1.25‡ (0.94–1.67) | 1.21 × 10−1 | 1.42 (1.27–1.59) | 1.21 × 10−9 | 0 | 0.61 |
| 15q25.1 | IREB2 | rs2009746 | G | 0.37 | 0.21 | 1.38‡ (1.20–1.60) | 1.30 × 10−5 | 1.59‡ (1.26–2.00) | 8.33 × 10−5 | 1.32‡ (0.99–1.75) | 5.82 × 10−2 | 1.42 (1.27–1.59) | 1.32 × 10−9 | 0 | 0.52 |
| 15q25.1 | CHRNA5 | rs2036527 | A | 0.38 | 0.23 | 1.44 (1.24–1.67) | 1.05 × 10−6 | 1.43 (1.14–1.79) | 1.93 × 10−3 | 1.25‡ (0.94–1.67) | 1.23 × 10−1 | 1.41 (1.26–1.57) | 3.15 × 10−9 | 0 | 0.69 |
| 15q25.1 | CHRNA5 | rs55781567 | G | 0.37 | 0.28 | 1.44‡ (1.24–1.67) | 1.22 × 10−6 | 1.42‡ (1.14–1.78) | 1.94 × 10−3 | 1.25‡ (0.94–1.66) | 1.25 × 10−1 | 1.40 (1.25–1.57) | 3.68 × 10−9 | 0 | 0.69 |
| 15q25.1 | AGPHD1 | rs8031948 | T | 0.38 | 0.17 | 1.43‡ (1.23–1.65) | 1.89 × 10−6 | 1.51‡ (1.17–1.94) | 1.36 × 10−3 | 1.27‡ (0.95–1.68) | 1.03 × 10−1 | 1.42 (1.26–1.59) | 3.74 × 10−9 | 0 | 0.65 |
| 15q25.1 | CHRNA5 | rs190065944 | A | 0.29 | 0.23 | 1.67‡ (1.35–2.07) | 2.05 × 10−6 | 1.57‡ (1.18–2.09) | 1.96 × 10−3 | 1.36‡ (0.90–2.06) | 1.41 × 10−1 | 1.59 (1.36–1.86) | 7.04 × 10−9 | 0 | 0.69 |
| 15q25.1 | AGPHD1 | rs8034191 | C | 0.38 | 0.17 | 1.43 (1.24–1.66) | 1.75 × 10−6 | 1.44 (1.13–1.84) | 3.49 × 10−3 | 1.26 (0.95–1.67) | 1.09 × 10−1 | 1.40 (1.25–1.57) | 7.80 × 10−9 | 0 | 0.72 |
| 15q25.1 | IREB2 | rs56219465 | G | 0.37 | 0.23 | 1.39‡ (1.20–1.60) | 1.19 × 10−5 | 1.43‡ (1.15–1.79) | 1.59 × 10−3 | 1.31‡ (0.99–1.75) | 5.89 × 10−2 | 1.39 (1.24–1.55) | 1.20 × 10−8 | 0 | 0.90 |
| 15q25.1 | IREB2 | rs72738718 | C | 0.37 | 0.23 | 1.39‡ (1.20–1.61) | 1.16 × 10−5 | 1.43‡ (1.14–1.79) | 1.65 × 10−3 | 1.31‡ (0.99–1.75) | 6.01 × 10−2 | 1.39 (1.24–1.55) | 1.21 × 10−8 | 0 | 0.90 |
| 15q25.1 | IREB2 | rs7181486 | C | 0.37 | 0.23 | 1.39‡ (1.20–1.60) | 1.18 × 10−5 | 1.43‡ (1.15–1.79) | 1.61 × 10−3 | 1.31‡ (0.99–1.75) | 5.88 × 10−2 | 1.39 (1.24–1.55) | 1.21 × 10−8 | 0 | 0.90 |
| 15q25.1 | IREB2 | rs17483929 | A | 0.38 | 0.23 | 1.39 (1.20–1.60) | 1.19 × 10−5 | 1.43 (1.14–1.79) | 1.68 × 10−3 | 1.31‡ (0.99–1.75) | 5.89 × 10−2 | 1.39 (1.24–1.55) | 1.25 × 10−8 | 0 | 0.90 |
| 15q25.1 | AGPHD1 | rs11852372 | C | 0.35 | 0.17 | 1.45‡ (1.25–1.70) | 2.03 × 10−6 | 1.42‡ (1.10–1.82) | 6.25 × 10−3 | 1.27‡ (0.94–1.72) | 1.14 × 10−1 | 1.41 (1.25–1.59) | 1.57 × 10−8 | 0 | 0.75 |
| 15q25.1 | IREB2 | rs55983731 | T | 0.37 | 0.23 | 1.39‡ (1.20–1.60) | 1.18 × 10−5 | 1.41‡ (1.12–1.76) | 2.97 × 10−3 | 1.31‡ (0.99–1.75) | 5.87 × 10−2 | 1.38 (1.23–1.54) | 2.01 × 10−8 | 0 | 0.93 |
| 15q25.1 | IREB2 | rs17483686 | T | 0.37 | 0.23 | 1.39‡ (1.20–1.60) | 1.19 × 10−5 | 1.41‡ (1.12–1.76) | 2.98 × 10−3 | 1.31‡ (0.99–1.75) | 5.87 × 10−2 | 1.38 (1.23–1.54) | 2.06 × 10−8 | 0 | 0.93 |
| 15q25.1 | IREB2 | rs17483721 | C | 0.61 | 0.77 | 1.39 (1.20–1.60) | 1.21 × 10−5 | 1.40 (1.12–1.76) | 3.01 × 10−3 | 1.31‡ (0.99–1.75) | 5.87 × 10−2 | 1.38 (1.23–1.54) | 2.16 × 10−8 | 0 | 0.93 |
| 15q25.1 | CHRNA3 | rs56077333 | A | 0.35 | 0.17 | 1.46‡ (1.25–1.70) | 1.63 × 10−6 | 1.41‡ (1.09–1.83) | 7.98 × 10−3 | 1.24‡ (0.92–1.68) | 1.58 × 10−1 | 1.41 (1.25–1.59) | 2.38 × 10−8 | 0 | 0.65 |
| 15q25.1 | IREB2 | rs72738736 | T | 0.37 | 0.23 | 1.38‡ (1.19–1.59) | 1.79 × 10−5 | 1.42‡ (1.13–1.77) | 2.50 × 10−3 | 1.32‡ (0.99–1.75) | 5.72 × 10−2 | 1.38 (1.23–1.54) | 2.54 × 10−8 | 0 | 0.93 |
Definition of abbreviations: AA, African American; CI, confidence interval; COPDGene, Genetic Epidemiology of COPD Study; ECLIPSE, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; EUR, European white; FRQ, risk allele frequency; I2, percentage of the variability in effect estimates due to heterogeneity; NHW, non-Hispanic white; OR, odds ratio; Q, P values for Cochran’s Q test; SNP, single-nucleotide polymorphism.
Adjusted for age, sex, pack-years of cigarette smoking and genetic ancestry, as summarized in the principal components.
EUR frequency data is from the meta-analysis of COPDGene NHW and ECLIPSE.
Imputed genotypes.