Power calculations were undertaken using Quanto (see URLs) (Supplementary Figure 9). For stage 1, genome-wide association studies of FEV1, FVC and FEV1/FVC were undertaken separately in heavy-smokers and never-smokers and then meta-analysed for each trait. Linear regression of age, age2, sex, height, the first 10 principal components of genetic ancestry and pack years of smoking (in smokers) on each trait was undertaken and residuals were ranked and transformed to inverse normally distributed Z-scores. For the first 26 lung function variants reported11,13,14,50 we showed Stage 2 effect size estimates14 were comparable with those from inverse normally distributed Z-scores in UK BiLEVE (Supplementary Figure 10). Subsequently these Z-scores were used for genome-wide association testing using an additive genetic model (SNPTEST v2.5). The full genome-wide stage 1 results are available via UK Biobank (see URLs).
