Association of family history and PRS with outcomes (left)
| Outcome | Covariates | COPDGene NHW | COPDGene AA | ECLIPSE | |||||||||
| Family history (OR or beta (95% CI)) | P value | PRS (OR or beta (95% CI)) | P value | Family history (OR or beta (95% CI)) | P value | PRS (OR or beta (95% CI)) | P value | Family history (OR or beta (95% CI)) | P value | PRS (OR or beta (95% CI)) | P value | ||
| 6 min walk distance | Height, weight | −27 (−49 to −5.4) | 0.016 | −33 (−43 to −23) | 1.40E-10 | −36 (−75 to 3.2) | 0.076 | −17 (−32 to −2.5) | 0.019 | −29 (−66 to 8.2) | 0.14 | 2.1 (−16 to 20) | 0.82 |
| SGRQ Total Score | 0.27 (0.21 to 0.33) | 1.20E-16 | 0.14 (0.11 to 0.17) | 3.00E-21 | 0.39 (0.26 to 0.52) | 5.80E-09 | 0.061 (0.014 to 0.11) | 0.011 | 3.6 (1.4 to 5.8) | 0.00084 | 2.2 (1.2 to 3.2) | 2.70E-05 | |
| Frequent Exacerbations | FEV1 % predicted, current smoking | 1.65 (1.26 to 2.16) | 0.00031 | 0.91 (0.79 to 1.04) | 0.18 | 1.39 (0.83 to 2.34) | 0.21 | 1.2 (0.96 to 1.5) | 0.11 | 1.2 (0.94 to 1.52) | 0.15 | 0.99 (0.88 to 1.11) | 0.83 |
| Severe Exacerbations | FEV1 % predicted, current smoking | 1.17 (0.91 to 1.49) | 0.22 | 0.97 (0.86 to 1.1) | 0.66 | 1.35 (0.89 to 2.03) | 0.15 | 1.04 (0.88 to 1.24) | 0.64 | 0.96 (0.74 to 1.24) | 0.76 | 1.04 (0.93 to 1.18) | 0.48 |
| BODE | 0.43 (0.3 to 0.56) | 5.10E-11 | 0.38 (0.32 to 0.44) | 4.10E-35 | 0.61 (0.39 to 0.83) | 5.40E-08 | 0.19 (0.11 to 0.27) | 3.70E-06 | 0.13 (-0.086 to 0.35) | 0.24 | 0.053 (-0.051 to 0.16) | 0.32 | |
| Dead | BODE | 1.15 (0.96 to 1.36) | 0.12 | 1.14 (1.05 to 1.24) | 0.0016 | 1.06 (0.71 to 1.59) | 0.76 | 1.22 (1.05 to 1.41) | 0.0089 | 1.17 (0.94 to 1.44) | 0.16 | 1.01 (0.92 to 1.12) | 0.78 |
| % LAA < -950 HU | CT scanner | 0.37 (0.29 to 0.45) | 1.10E-19 | 0.19 (0.15 to 0.23) | 6.00E-24 | 0.32 (0.17 to 0.47) | 4.30E-05 | 0.044 (-0.011 to 0.099) | 0.11 | 0.12 (0.01 to 0.23) | 0.032 | 0.11 (0.059 to 0.16) | 3.80E-05 |
| Perc15 | CT scanner | −6.1 (-7.6 to -4.6) | 1.20E-15 | −3.4 (-4.1 to -2.7) | 1.10E-21 | −5.9 (-9.2 to -2.6) | 0.00039 | −1.4 (-2.6 to -0.24) | 0.015 | −2.4 (-5.3 to 0.54) | 0.097 | −2.5 (-3.8 to -1.2) | 0.00028 |
| Pi10 | CT scanner | 0.0092 (0.0016 to 0.017) | 0.017 | 0.013 (0.0095 to 0.017) | 2.30E-13 | −0.0073 (-0.022 to 0.0072) | 0.32 | 0.0069 (0.0018 to 0.012) | 0.0091 | −0.00037 (−0.018 to 0.017) | 0.97 | 0.0034 (−0.0046 to 0.011) | 0.4 |
| WA% | CT scanner | 0.35 (0.17 to 0.53) | 0.00015 | 0.75 (0.67 to 0.83) | 5.00E-66 | 0.29 (−0.082 to 0.66) | 0.11 | 0.51 (0.38 to 0.64) | 3.10E-14 | 0.15 (−0.28 to 0.58) | 0.5 | 0.82 (0.62 to 1) | 6.40E-16 |
| Paraseptal emphysema | CT scanner | 1.57 (1.17 to 2.11) | 0.0029 | 1.5 (1.29 to 1.74) | 6.20E-08 | 1.68 (1.04 to 2.7) | 0.034 | 1.05 (0.88 to 1.27) | 0.57 | NA | NA | NA | NA |
| Bronchial airway disease | CT scanner | 1.19 (0.83 to 1.71) | 0.34 | 1.64 (1.38 to 1.95) | 2.30E-08 | 0.77 (0.39 to 1.49) | 0.44 | 1.25 (1 to 1.57) | 0.051 | NA | NA | NA | NA |
| Small airway disease | CT scanner | 1.04 (0.68 to 1.57) | 0.87 | 1.79 (1.47 to 2.17) | 6.00E-09 | 1.71 (0.71 to 4.14) | 0.23 | 1.04 (0.72 to 1.52) | 0.82 | NA | NA | NA | NA |
| Mild CLE | CT scanner | 1.57 (1.22 to 2.03) | 0.00053 | 1.41 (1.25 to 1.6) | 4.20E-08 | 0.83 (0.48 to 1.43) | 0.51 | 1.15 (0.95 to 1.39) | 0.15 | NA | NA | NA | NA |
| Upper lobe CLE | CT scanner | 2.35 (1.46 to 3.77) | 0.00042 | 1.83 (1.42 to 2.35) | 2.50E-06 | 2.86 (0.94 to 8.73) | 0.064 | 0.91 (0.52 to 1.58) | 0.73 | NA | NA | NA | NA |
| Lower lobe CLE | CT scanner | 7.76 (2.19 to 27.41) | 0.0015 | 2.41 (1.3 to 4.47) | 0.005 | * | * | * | * | NA | NA | NA | NA |
| Diffuse CLE | CT scanner | 2.42 (1.64 to 3.57) | 9.10E-06 | 2 (1.63 to 2.45) | 3.70E-11 | 0.86 (0.27 to 2.72) | 0.79 | 0.88 (0.56 to 1.39) | 0.59 | NA | NA | NA | NA |
| Visual without quantitative emphysema | CT scanner | 2.12 (1.39 to 3.24) | 0.00051 | 1.65 (1.34 to 2.03) | 2.50E-06 | 1.31 (0.64 to 2.68) | 0.46 | 1.22 (0.89 to 1.67) | 0.21 | NA | NA | NA | NA |
| Quantitative without visual emphysema | CT scanner | 1.66 (0.87 to 3.17) | 0.13 | 1.54 (1.11 to 2.13) | 0.01 | * | * | * | * | NA | NA | NA | NA |
All models had form outcome ~family history+PRS+age+sex + pack-years+principal components of genetic ancestry+C, where C equals any additional covariates listed in the table for a specific outcome.21 % LAA ≤950 HU=per cent low attenuation area of the lung less than −950 HU. Perc15=15th percentile of the lung density histogram on inspiratory scans. Pi10=square root of wall area of a hypothetical airway with an internal perimeter of 10 mm. The PRS was treated as a continuous variable, and ORs are associated with 1 SD increase in the risk score.
*Indicates that model did not converge as certain phenotypes had few numbers of participants.
BODE, body mass index, obstruction, dyspnoea, exercise capacity index; CLE, centrilobular emphysema; FEV1, forced expiratory volume in 1 s; HU, Hounsfield units; LAA, low attenuation area; PRS, Polygenic Risk Score; SGRQ, St. George Respiratory Questionnaire; WA%, mean wall area per cent.