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

TitleNew genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.
Publication TypeJournal Article
Year of Publication2019
AuthorsShrine, N, Guyatt, AL, A Erzurumluoglu, M, Jackson, VE, Hobbs, BD, Melbourne, CA, Batini, C, Fawcett, KA, Song, K, Sakornsakolpat, P, Li, X, Boxall, R, Reeve, NF, Obeidat, M'en, Zhao, JHua, Wielscher, M, 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, Lehtimäki, T, Allen, RJ, Bakke, PS, Beaty, TH, Bleecker, ER, Bossé, Y, Brandsma, C-A, 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, X, Li, L, Lin, K, Lind, L, Locantore, N, Luan, J'an, 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, Artigas, MSoler, Sparrow, D, Tal-Singer, R, Timmers, PRHJ, Van den Berge, M, Whittaker, JC, Woodruff, PG, Yerges-Armstrong, LM, Troyanskaya, OG, Raitakari, OT, Kähönen, M, Polašek, O, Gyllensten, U, Rudan, I, Deary, IJ, Probst-Hensch, NM, Schulz, H, James, AL, Wilson, JF, Stubbe, B, Zeggini, E, Jarvelin, M-R, 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
Corporate Authors
JournalNat Genet
Volume51
Issue3
Pagination481-493
Date Published2019 03
ISSN1546-1718
Abstract

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.

DOI10.1038/s41588-018-0321-7
Alternate JournalNat. Genet.
PubMed ID30804560
PubMed Central IDPMC6397078
Grant List / / Wellcome Trust / United Kingdom
K08 HL136928 / HL / NHLBI NIH HHS / United States
R01 HL113264 / HL / NHLBI NIH HHS / United States