Meta-analyses across large population-based cohorts have previously reported an association at 1q41, near TGFB2, with FEV1 /FVC ratio56. However, the lead SNP for this association, rs993925, is not in strong LD (r2=0•027 in EUR) and lies over 250kb away from the SNPs reported here. Our top association is, however, in strong LD (r2=0•97 in EUR) with rs6684205, recently identified as an expression quantitative trait loci (eQTL) for TGFB2 in lung tissue57. The COPD risk allele has been associated with decreased expression, consistent with our findings of decreased TGFB2 expression in lung tissue from severe COPD cases versus controls. These lines of evidence strongly suggest effects of this locus on COPD susceptibility operate via changes in lung TGFB2 expression. While genetic variants in or near TGFB1 have been studied in association with COPD58–60, an association of variants near TGFB2 with COPD has not been previously described. Tgfb2 null mice have dilated conducting airways and collapsed terminal and respiratory bronchioles61, and loss-of-function mutations in TGFB2 have been associated with Loeys-Dietz syndrome, a disorder of connective tissue showing phenotypic overlap with Marfan syndrome,
