To test the single variant associations with COPD susceptibility and risk of exacerbation, logistic regression using age, age2, sex, and height as covariates (unless otherwise indicated, Supplementary Note) and assuming an additive genetic effect was used. To test the joint effect of these variants, risk alleles in the subset of the 95 signals with data available in each study (from 86 to 95) were summed to create an unweighted genetic risk score and logistic regression was used to test the effect of the risk score, as a continuous variable, on COPD status and COPD exacerbation status (adjusted for age, age2, sex and height, unless otherwise indicated, Supplementary Note). Results, both from single variant and risk scores, were meta-analysed separately for studies where similar study design and phenotyping was used: eMR, case-control and lung resection, and results were also meta-analysed across studies. Inverse variance weighted meta-analysis was used. In CKB, analyses were adjusted for sex, age, age2, height, region (n=10) and disease status (n=5) and final results were GC-corrected based on genome-wide inflation estimates. Heterogeneity was tested using I2(ref 58).
