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 with the inverted haplotype.42,43 The inversion locus contains structural variation resulting from three duplication events (150–300 kb).42,43 We imputed the nine common structural haplotypes (appendix pp 23–24)42 and found that the number of copies of the 150 kb region containing the 5′ end of KANSL1 (the entire 150 kb duplication region found only in individuals who carry the inversion and a nested region of the 300 kb duplication region found only in individuals who do not carry the inversion) was associated with extremes of FEV1 (p=2·40 × 10−6; appendix p 71). The sentinel SNP rs2532349 lies within this region.
