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

Shrine, NORCID logo; Guyatt, ALORCID logo; Erzurumluoglu, AM; Jackson, VE; Hobbs, BDORCID logo; Melbourne, CA; Batini, C; Fawcett, KA; Song, K; Sakornsakolpat, PORCID logo; +100 more...Li, X; Boxall, R; Reeve, NF; Obeidat, MORCID logo; Zhao, JH; Wielscher, M; Weiss, SORCID logo; Kentistou, KAORCID logo; Cook, JP; Sun, BBORCID logo; Zhou, J; Hui, J; Karrasch, S; Imboden, M; Harris, SE; Marten, J; Enroth, SORCID logo; Kerr, SM; Surakka, I; Vitart, VORCID logo; Lehtimäki, T; Allen, RJORCID logo; Bakke, PS; Beaty, THORCID logo; Bleecker, ER; Bossé, YORCID logo; Brandsma, C; Chen, Z; Crapo, JD; Danesh, J; DeMeo, DL; Dudbridge, FORCID logo; Ewert, R; Gieger, C; Gulsvik, A; Hansell, AL; Hao, K; Hoffman, JD; Hokanson, JE; Homuth, G; Joshi, PKORCID logo; Joubert, P; Langenberg, C; Li, X; Li, L; Lin, K; Lind, L; Locantore, N; Luan, J; Mahajan, AORCID logo; Maranville, JC; Murray, AORCID logo; Nickle, DC; Packer, R; Parker, MM; Paynton, ML; Porteous, DJORCID logo; Prokopenko, D; Qiao, D; Rawal, R; Runz, H; Sayers, IORCID logo; Sin, DD; Smith, BHORCID logo; Soler Artigas, M; Sparrow, D; Tal-Singer, RORCID logo; Timmers, PRORCID logo; Van den Berge, M; Whittaker, JC; Woodruff, PG; Yerges-Armstrong, LM; Troyanskaya, OGORCID logo; Raitakari, OT; Kähönen, M; Polašek, O; Gyllensten, U; Rudan, IORCID logo; Deary, IJ; Probst-Hensch, NM; Schulz, H; James, AL; Wilson, JFORCID logo; Stubbe, B; Zeggini, EORCID logo; Jarvelin, M; Wareham, N; Silverman, EK; Hayward, CORCID logo; Morris, APORCID logo; Butterworth, ASORCID logo; Scott, RA; Walters, RGORCID logo; Meyers, DA; Cho, MHORCID logo; Strachan, DPORCID logo; Hall, IP; Tobin, MDORCID logo; Wain, LVORCID logo; Understanding Society Scientific Group and (2019) New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. NATURE GENETICS, 51 (3). pp. 481-493. ISSN 1061-4036 DOI: 10.1038/s41588-018-0321-7
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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.


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