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
KeywordsAged, Aged, 80 and over, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Lung, Male, Middle Aged, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, Risk Factors, Smoking
Abstract

<p>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.</p>

DOI10.1038/s41588-018-0321-7
Alternate JournalNat Genet
PubMed ID30804560
PubMed Central IDPMC6397078
Grant ListRG/18/13/33946 / BHF_ / British Heart Foundation / United Kingdom
RG/13/13/30194 / BHF_ / British Heart Foundation / United Kingdom
MR/N011317/1 / MRC_ / Medical Research Council / United Kingdom
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
MC_PC_14135 / MRC_ / Medical Research Council / United Kingdom
MC_UU_00017/1 / MRC_ / Medical Research Council / United Kingdom
K08 HL136928 / HL / NHLBI NIH HHS / United States
BB/F019394/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
MC_PC_13049 / MRC_ / Medical Research Council / United Kingdom
MC_UU_00007/10 / MRC_ / Medical Research Council / United Kingdom
R01 HL113264 / HL / NHLBI NIH HHS / United States
MC_U137686851 / MRC_ / Medical Research Council / United Kingdom
G1001799 / MRC_ / Medical Research Council / United Kingdom
R01 HL089897 / HL / NHLBI NIH HHS / United States
212946/Z/18/Z / WT_ / Wellcome Trust / United Kingdom
MR/N01104X/2 / MRC_ / Medical Research Council / United Kingdom
U01 HL089897 / HL / NHLBI NIH HHS / United States
G1000861 / MRC_ / Medical Research Council / United Kingdom
MC_UU_12026/2 / MRC_ / Medical Research Council / United Kingdom
MC_PC_12010 / MRC_ / Medical Research Council / United Kingdom
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
U01 HL089856 / HL / NHLBI NIH HHS / United States
MR/N01104X/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL135142 / HL / NHLBI NIH HHS / United States
MR/S003762/1 / MRC_ / Medical Research Council / United Kingdom
G0700704 / MRC_ / Medical Research Council / United Kingdom
/ WT_ / Wellcome Trust / United Kingdom