| Title | New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | Shrine, 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 | |
| Journal | Nat Genet |
| Volume | 51 |
| Issue | 3 |
| Pagination | 481-493 |
| Date Published | 2019 Mar |
| ISSN | 1546-1718 |
| Keywords | Aged, 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> |
| DOI | 10.1038/s41588-018-0321-7 |
| Alternate Journal | Nat Genet |
| PubMed ID | 30804560 |
| PubMed Central ID | PMC6397078 |
| Grant List | R01 HL113264 / HL / NHLBI NIH HHS / United States R01 HL089897 / HL / NHLBI NIH HHS / United States 212946/Z/18/Z / / Wellcome Trust / United Kingdom RG/13/13/30194 / BHF_ / British Heart Foundation / United Kingdom MC_UU_12026/2 / MRC_ / Medical Research Council / United Kingdom MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom MR/N01104X/1 / MRC_ / Medical Research Council / United Kingdom MC_UU_00017/1 / MRC_ / Medical Research Council / United Kingdom G1000861 / MRC_ / Medical Research Council / United Kingdom MC_U137686851 / MRC_ / Medical Research Council / United Kingdom / / Wellcome Trust / United Kingdom MC_PC_14135 / MRC_ / Medical Research Council / United Kingdom RG/18/13/33946 / BHF_ / British Heart Foundation / United Kingdom BB/F019394/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom U01 HL089897 / HL / NHLBI NIH HHS / United States MR/N01104X/2 / MRC_ / Medical Research Council / United Kingdom G1001799 / MRC_ / Medical Research Council / United Kingdom G0700704 / MRC_ / Medical Research Council / United Kingdom R01 HL111024 / HL / NHLBI NIH HHS / United States U01 HL089856 / HL / NHLBI NIH HHS / United States R01 HL135142 / HL / NHLBI NIH HHS / United States MC_PC_12010 / MRC_ / Medical Research Council / United Kingdom MC_UU_00007/10 / MRC_ / Medical Research Council / United Kingdom K08 HL136928 / HL / NHLBI NIH HHS / United States K01 HL129039 / HL / NHLBI NIH HHS / United States MR/S003762/1 / MRC_ / Medical Research Council / United Kingdom MR/N011317/1 / MRC_ / Medical Research Council / United Kingdom MC_PC_13049 / MRC_ / Medical Research Council / United Kingdom |
