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

Shrine, N; Guyatt, AL; Erzurumluoglu, AM; Jackson, VE; Hobbs, BD; Melbourne, C; Batini, C; Fawcett, KA; Song, K; Sakornsakolpat, P; et al. Shrine, N; Guyatt, AL; Erzurumluoglu, AM; Jackson, VE; Hobbs, BD; Melbourne, C; Batini, C; Fawcett, KA; Song, K; Sakornsakolpat, P; Li, X; Boxall, R; Reeve, NF; Obeidat, M; Zhao, JH; Wielscher, M; Understanding Society Scientific Group; 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, J; Homuth, G; Joshi, PK; Joubert, P; Langenberg, C; Li, X; 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, D; 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 de Berge, M; Whittaker, JC; Woodruff, P; 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 (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 https://doi.org/10.1038/s41588-018-0321-7
SGUL Authors: Strachan, David Peter

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Abstract

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.

Item Type: Article
Additional Information: This is a post-peer-review, pre-copyedit version of an article published in Nature Genetics. The final authenticated version is available online at: http://dx.doi.org/10.1038/s41588-018-0321-7 Corrections available at https://doi.org/10.1038/s41588-019-0438-3 and https://doi.org/10.1038/s41588-024-01752-4
Keywords: 11 Medical And Health Sciences, 06 Biological Sciences, Developmental Biology
SGUL Research Institute / Research Centre: Academic Structure > Population Health Research Institute (INPH)
Journal or Publication Title: NATURE GENETICS
ISSN: 1061-4036
Dates:
DateEvent
25 February 2019Published
27 November 2018Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
K08 HL136928National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
633212Horizon 2020UNSPECIFIED
ES/H029745/1Economic and Social Research Councilhttp://dx.doi.org/10.13039/501100000269
MR/K50127X/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G1000861Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
WT098051Wellcome Trusthttp://dx.doi.org/10.13039/100004440
WT098017Wellcome Trusthttp://dx.doi.org/10.13039/100004440
WT064890Wellcome Trusthttp://dx.doi.org/10.13039/100004440
R01HL113264National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01HL137927National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01HL135142National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
WT202849/Z/16/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
MR/N011317/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
202922/Z/16/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
088158/Z/09/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
104085/Z/14/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
MC_PC_13049Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_PC_14135Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
RE/13/1/30181British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
076113/B/04/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
079895Wellcome Trusthttp://dx.doi.org/10.13039/100004440
MR/K026992/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
084703MAWellcome Trusthttp://dx.doi.org/10.13039/100004440
104036/Z/14/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
G0500539Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0600705Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G1002319Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/M013138/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
WT064890Wellcome Trusthttp://dx.doi.org/10.13039/100004440
WT098017Wellcome Trusthttp://dx.doi.org/10.13039/100004440
ES/H029745/1Economic and Social Research Councilhttp://dx.doi.org/10.13039/501100000269
G0800270Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
SP/09/002British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
URI: https://openaccess.sgul.ac.uk/id/eprint/110268
Publisher's version: https://doi.org/10.1038/s41588-018-0321-7

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