We included 14 studies of individuals of European ancestry, with sample sizes totaling 20,288 (Table 1). All individuals had measures of FEV1 and FVC and smoking status recorded. FEV1 and (separately) FEV1/FVC measures were adjusted for age, age2, sex, height and ancestry principal components within each study. Genome-wide genotyping was undertaken with a variety of platforms, and standard quality control measures were used (Online Methods and Supplementary Table 1). Genotypes were imputed for ~2.5 million autosomal SNPs from HapMap CEU data and tested for association separately for the inverse-normal transformed residuals of FEV1 and FEV1/FVC under an additive genetic model. We carried out meta-analysis of study-specific test statistics using an inverse variance weighting. We applied genomic control at the study and meta-analysis levels to avoid overinflation of test statistics owing to population structure or relatedness. Test statistic inflation before applying genomic control at the meta-analysis level was modest (λGC = 1.046 for FEV1 and 1.035 for FEV1/FVC). The plots of meta-analysis test statistics against expected values under the null hypothesis showed an excess of extreme values even after exclusion of the previously reported11 4q31 locus near HHIP, indicative of additional loci associated with lung function (Supplementary Fig. 1a,b).
