New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.
Nature genetics 2018 ; 51: 481-493.
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, 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 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, Kähönen M, Polasek O, Gyllensten U, Rudan I, Deary IJ, Probst-Hensch NM, Schulz H, James AL, Wilson JF, Stubbe B, Zeggini E, Järvelin 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, and Understanding Society Scientific Group
PubMed ID : 30804560
PMCID : 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.