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New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries


Shrine, N; Guyatt, AL; Erzurumluoglu, AM; Jackson, VE; Hobbs, BD; Melbourne, CA; Batini, C; Fawcett, KA; Song, K; Sakornsakolpat, P; Li, X; Boxall, R; Reeve, NF; Obeidat, M; Zhao, JH; Wielscher, M; Understanding Society Scientific Group,; Weiss, S; Kentistou, KA; Cook, JP; Sun, BB; Zhou, J; Hui, J; Karrasch, S; Imboden, M; Harris, SE; Marten, J; Enroth, S; Kerr, SM; Surakka, I; Vitart, V; Lehtimaki, T; Allen, RJ; Bakke, PS; Beaty, TH; Bleecker, ER; Bosse, Y; Brandsma, CA; Chen, Z; Crapo, JD; Danesh, J; DeMeo, DL; Dudbridge, F; Ewert, R; Gieger, C; Gulsvik, A; Hansell, AL; Hao, K; Hoffman, JD; Hokanson, JE; Homuth, G; Joshi, PK; Joubert, P; Langenberg, C; Li, L; Lin, K; Lind, L; Locantore, N; Luan, J; Mahajan, A; Maranville, JC; Murray, A; Nickle, DC; Packer, R; Parker, MM; Paynton, ML; Porteous, DJ; Prokopenko, D; Qiao, D; Rawal, R; Runz, H; Sayers, I; Sin, DD; Smith, BH; Soler Artigas, M; Sparrow, D; Tal-Singer, R; Timmers, Prhj; Van den Berge, M; Whittaker, JC; Woodruff, PG; Yerges-Armstrong, LM; Troyanskaya, OG; Raitakari, OT; Kahonen, M; Polasek, O; Gyllensten, U; Rudan, I; Deary, IJ; Probst-Hensch, NM; Schulz, H; James, AL; Wilson, JF; Stubbe, B; Zeggini, E; Jarvelin, MR; Wareham, N; Silverman, EK; Hayward, C; Morris, AP; Butterworth, AS; Scott, RA; Walters, RG; Meyers, DA; Cho, MH; Strachan, DP; Hall, IP; Tobin, MD; Wain, LV
2019-02-25
Nature Genetics
Journal Article
51
481-493
Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
Springer Nature
Population Health and Immunity
10.1038/s41588-018-0321-7
30804560
Refer to copyright notice on published article.