A1 Refereed original research article in a scientific journal
New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
Authors: Shrine N, Guyatt AL, Erzurumluoglu AM, Jackson VE, Hobbs BD, Melbourne CA, Batini C, Fawcett KA, Song K, Sakornsakolpat P, Li XN, Boxall R, Reeve NF, Obeidat M, Zhao JH, 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, Lehtimaki T, Allen RJ, Bakke PS, Beaty TH, Bleecker ER, Bosse Y, Brandsma CA, Chen ZM, 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 LM, Lin K, Lind L, Locantore N, Luan JA, Mahajan A, Maranville JC, Murray A, Nickle DC, Packer R, Parker MM, Paynton ML, Porteous DJ, Prokopenko D, Qiao DD, Rawal R, Runz H, Sayers I, Sin DD, Smith BH, Artigas MS, Sparrow D, Tal-Singer R, Timmers PRHJ, Van den Berge M, Whittaker JC, Woodruff PG, Verges-Armstrong LM, Troyanskaya OG, Raitakari OT, Kahonenn 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, Tobin MD, Wain LV, Strachan DP, Hall IP
Publisher: NATURE PUBLISHING GROUP
Publication year: 2019
Journal: Nature Genetics
Journal name in source: NATURE GENETICS
Journal acronym: NAT GENET
Volume: 51
Issue: 3
First page : 481
Last page: 493
Number of pages: 16
ISSN: 1061-4036
DOI: https://doi.org/10.1038/s41588-018-0321-7
Self-archived copy’s web address: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397078/
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.
