Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
- Wain, L.V.
- Shrine, N.
- Artigas, M.S.
- Erzurumluoglu, A.M.
- Noyvert, B.
- Bossini-Castillo, L.
- Obeidat, M.
- Henry, A.P.
- Portelli, M.A.
- Hall, R.J.
- Billington, C.K.
- Rimington, T.L.
- Fenech, A.G.
- John, C.
- Blake, T.
- Jackson, V.E.
- Allen, R.J.
- Prins, B.P.
- Campbell, A.
- Porteous, D.J.
- Jarvelin, M.R.
- Wielscher, M.
- James, A.L.
- Hui, J.
- Wareham, N.J.
- Zhao, J.H.
- Wilson, J.F.
- Joshi, P.K.
- Stubbe, B.
- Rawal, R.
- Schulz, H.
- Imboden, M.
- Probst-Hensch, N.M.
- Karrasch, S.
- Gieger, C.
- Deary, I.J.
- Harris, S.E.
- Marten, J.
- Rudan, I.
- Enroth, S.
- Gyllensten, U.
- Kerr, S.M.
- Polasek, O.
- Kähönen, M.
- Surakka, I.
- Vitart, V.
- Hayward, C.
- Lehtimäki, T.
- Raitakari, O.T.
- Evans, D.M.
- Henderson, A.J.
- Pennell, C.E.
- Wang, C.A.
- Sly, P.D.
- Wan, E.S.
- Busch, R.
- Hobbs, B.D.
- Litonjua, A.A.
- Sparrow, D.W.
- Gulsvik, A.
- Bakke, P.S.
- Crapo, J.D.
- Beaty, T.H.
- Hansel, N.N.
- Mathias, R.A.
- Ruczinski, I.
- Barnes, K.C.
- Bossé, Y.
- Joubert, P.
- van den Berge, M.
- Brandsma, C.A.
- Paré, P.D.
- Sin, D.D.
- Nickle, D.C.
- Hao, K.
- Gottesman, O.
- Dewey, F.E.
- Bruse, S.E.
- Carey, D.J.
- Kirchner, H.L.
- Jonsson, S.
- Thorleifsson, G.
- Jonsdottir, I.
- Gislason, T.
- Stefansson, K.
- Schurmann, C.
- Nadkarni, G.
- Bottinger, E.P.
- Loos, R.J.
- Walters, R.G.
- Chen, Z.
- Millwood, I.Y.
- Vaucher, J.
- Kurmi, O.P.
- Li, L.
- Hansell, A.L.
- Brightling, C.
- Zeggini, E.
- Cho, M.H.
- Silverman, E.K.
- Sayers, I.
- Trynka, G.
- Morris, A.P.
- Strachan, D.P.
- Hall, I.P.
- Tobin, M.D.
DOIAbstract
Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes...
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