Using a risk score based on the available 95 sentinel variants or their best proxies, and using data from up to 9791 COPD cases and 120,462 controls (Online Methods), for the meta-analysis the OR (95% CI) per standard deviation change in risk score (~6 alleles) was 1.24 (1.20-1.27), P=5.05x10-49 (Figure 2a, Supplementary Table 11). We observed considerable heterogeneity in effect estimates between the different COPD studies (I2=92%) which had different approaches to ascertainment of COPD cases and variable disease severity. In UK Biobank (including UK BiLEVE) we found broadly similar effect size estimates of moderate-severe COPD to those in COPD case-control studies employing post-bronchodilator spirometry (OR=1.42 versus 1.36) and therefore we undertook further modelling showing a gradation in susceptibility to moderate-severe COPD across deciles of allelic risk score (Online Methods). The risk of moderate-severe COPD was more than three times higher in the top decile than the bottom decile (OR 3.71, 95% CI 3.34 to 4.12, Figure 2b). The estimated proportion of COPD cases attributable to allelic risk scores above the first decile (population attributable risk fraction) was 48.0% (95% CI 43.6 to 52.2%).
