We noted a broad signal of association (∼1·5 Mb) in an inversion locus at 17q21.31 (rs2532349, near KANSL1; appendix p 97). This signal was strongest in never smokers (rs2532349, p=1·66 × 10−10), but was also detected in heavy smokers (p=1·47 × 10−5). Genes in this locus, which include MAPT and CRHR1, have previously been associated with pulmonary fibrosis39,40 and inhaled corticosteroid response in asthma.41 SNP rs2532349 (and SNPs in strong linkage disequilibrium [r2>0·8]) was associated with mRNA expression levels of at least 15 genes in lung and blood (appendix pp 63–70). We identified differential expression for six genes at 17q21.31 during fetal lung development (and for four genes on different chromosomes regulated by trans eQTLs at 17q21.41; appendix pp 58–59). Relatively abundant novel transcripts (ie, compared with other transcripts detected) were identified by RNA sequencing in human bronchial epithelial cells for WNT3 and LRRC37A4P; expression of both genes was associated with rs2532349 in lung and blood (appendix pp 104–109). The SNP rs2532349 (MAF=24%) was in linkage disequilibrium with the inversion (r2>0.9); the allele associated with low FEV1 was positively correlated
