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

Understanding Society Scientific Group; Nick Shrine; Anna L. Guyatt; A. Mesut Erzurumluoglu; Victoria E. Jackson; Brian D. Hobbs; Carl A. Melbourne; Chiara Batini; Katherine A. Fawcett; Kijoung Song; Phuwanat Sakornsakolpat; Xingnan Li; Ruth Boxall; Nicola F. Reeve; Ma'en Obeidat; Jing Hua Zhao; Matthias Wielscher; Stefan Weiss; Katherine A. Kentistou; James P. Cook; Benjamin B. Sun; Jian Zhou; Jennie Hui; Stefan Karrasch; Medea Imboden; Sarah E. Harris; Jonathan Marten; Stefan Enroth; Shona M. Kerr; Ida Surakka; Veronique Vitart; Terho Lehtimäki; Richard J. Allen; Per S. Bakke; Terri H. Beaty; Eugene R. Bleecker; Yohan Bossé; Corry-Anke Brandsma; Zhengming Chen; James D. Crapo; John Danesh; Dawn L. DeMeo; Frank Dudbridge; Ralf Ewert; Christian Gieger; Amund Gulsvik; Anna L. Hansell; Ke Hao; Joshua D. Hoffman; John E. Hokanson; Blair H. Smith; Martin D. Tobin; Louise V. Wain

doi:10.1038/s41588-018-0321-7

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

Understanding Society Scientific Group
, Nick Shrine
, Anna L. Guyatt
, A. Mesut Erzurumluoglu
, Victoria E. Jackson
, Brian D. Hobbs
, Carl A. Melbourne
, Chiara Batini
, Katherine A. Fawcett
, Kijoung Song
, Phuwanat Sakornsakolpat
, Xingnan Li
, Ruth Boxall
, Nicola F. Reeve
, Ma'en Obeidat
, Jing Hua Zhao
, Matthias Wielscher
, Stefan Weiss
, Katherine A. Kentistou
, James P. Cook

Benjamin B. Sun, Jian Zhou, Jennie Hui, Stefan Karrasch, Medea Imboden, Sarah E. Harris, Jonathan Marten, Stefan Enroth, Shona M. Kerr, Ida Surakka, Veronique Vitart, Terho Lehtimäki, Richard J. Allen, Per S. Bakke, Terri H. Beaty, Eugene R. Bleecker, Yohan Bossé, Corry-Anke Brandsma, Zhengming Chen, James D. Crapo, John Danesh, Dawn L. DeMeo, Frank Dudbridge, Ralf Ewert, Christian Gieger, Amund Gulsvik, Anna L. Hansell, Ke Hao, Joshua D. Hoffman, John E. Hokanson (Lead / Corresponding author), Blair H. Smith, Martin D. Tobin (Lead / Corresponding author), Louise V. Wain (Lead / Corresponding author)

Population Health and Genomics

Research output: Contribution to journal › Article › peer-review

380 Citations (Scopus)

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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.

Original language	English
Pages (from-to)	481-493
Number of pages	13
Journal	Nature Genetics
Volume	51
Issue number	3
Early online date	25 Feb 2019
DOIs	https://doi.org/10.1038/s41588-018-0321-7
Publication status	Published - Mar 2019

ASJC Scopus subject areas

Genetics

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10.1038/s41588-018-0321-7

Author Accepted ManuscriptAccepted author manuscript, 775 KB
Author Accepted Manuscript: Supplementary InformationAccepted author manuscript, 5.28 MB
Author Accepted Manuscript: Figures 1-5Accepted author manuscript, 226 KB

Cite this

Understanding Society Scientific Group, Shrine, N., Guyatt, A. L., Erzurumluoglu, A. M., Jackson, V. E., Hobbs, B. D., Melbourne, C. A., Batini, C., Fawcett, K. A., Song, K., Sakornsakolpat, P., Li, X., Boxall, R., Reeve, N. F., Obeidat, M., Zhao, J. H., Wielscher, M., Weiss, S., Kentistou, K. A., ... Wain, L. V. (2019). New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. Nature Genetics, 51(3), 481-493. https://doi.org/10.1038/s41588-018-0321-7

@article{a62fb684d857414ea6277ffec19c7709,

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

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.",

author = "\{Understanding Society Scientific Group\} and Nick Shrine and Guyatt, \{Anna L.\} and Erzurumluoglu, \{A. Mesut\} and Jackson, \{Victoria E.\} and Hobbs, \{Brian D.\} and Melbourne, \{Carl A.\} and Chiara Batini and Fawcett, \{Katherine A.\} and Kijoung Song and Phuwanat Sakornsakolpat and Xingnan Li and Ruth Boxall and Reeve, \{Nicola F.\} and Ma'en Obeidat and Zhao, \{Jing Hua\} and Matthias Wielscher and Stefan Weiss and Kentistou, \{Katherine A.\} and Cook, \{James P.\} and Sun, \{Benjamin B.\} and Jian Zhou and Jennie Hui and Stefan Karrasch and Medea Imboden and Harris, \{Sarah E.\} and Jonathan Marten and Stefan Enroth and Kerr, \{Shona M.\} and Ida Surakka and Veronique Vitart and Terho Lehtim{\"a}ki and Allen, \{Richard J.\} and Bakke, \{Per S.\} and Beaty, \{Terri H.\} and Bleecker, \{Eugene R.\} and Yohan Boss{\'e} and Corry-Anke Brandsma and Zhengming Chen and Crapo, \{James D.\} and John Danesh and DeMeo, \{Dawn L.\} and Frank Dudbridge and Ralf Ewert and Christian Gieger and Amund Gulsvik and Hansell, \{Anna L.\} and Ke Hao and Hoffman, \{Joshua D.\} and Hokanson, \{John E.\} and Smith, \{Blair H.\} and Tobin, \{Martin D.\} and Wain, \{Louise V.\}",

year = "2019",

month = mar,

doi = "10.1038/s41588-018-0321-7",

language = "English",

volume = "51",

pages = "481--493",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

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Understanding Society Scientific Group, 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, 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, Smith, BH, Tobin, MD & Wain, LV 2019, 'New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries', Nature Genetics, vol. 51, no. 3, pp. 481-493. https://doi.org/10.1038/s41588-018-0321-7

TY - JOUR

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AU - Understanding Society Scientific Group

AU - Shrine, Nick

AU - Guyatt, Anna L.

AU - Erzurumluoglu, A. Mesut

AU - Jackson, Victoria E.

AU - Hobbs, Brian D.

AU - Melbourne, Carl A.

AU - Batini, Chiara

AU - Fawcett, Katherine A.

AU - Song, Kijoung

AU - Sakornsakolpat, Phuwanat

AU - Li, Xingnan

AU - Boxall, Ruth

AU - Reeve, Nicola F.

AU - Obeidat, Ma'en

AU - Zhao, Jing Hua

AU - Wielscher, Matthias

AU - Weiss, Stefan

AU - Kentistou, Katherine A.

AU - Cook, James P.

AU - Sun, Benjamin B.

AU - Zhou, Jian

AU - Hui, Jennie

AU - Karrasch, Stefan

AU - Imboden, Medea

AU - Harris, Sarah E.

AU - Marten, Jonathan

AU - Enroth, Stefan

AU - Kerr, Shona M.

AU - Surakka, Ida

AU - Vitart, Veronique

AU - Lehtimäki, Terho

AU - Allen, Richard J.

AU - Bakke, Per S.

AU - Beaty, Terri H.

AU - Bleecker, Eugene R.

AU - Bossé, Yohan

AU - Brandsma, Corry-Anke

AU - Chen, Zhengming

AU - Crapo, James D.

AU - Danesh, John

AU - DeMeo, Dawn L.

AU - Dudbridge, Frank

AU - Ewert, Ralf

AU - Gieger, Christian

AU - Gulsvik, Amund

AU - Hansell, Anna L.

AU - Hao, Ke

AU - Hoffman, Joshua D.

AU - Hokanson, John E.

AU - Smith, Blair H.

AU - Tobin, Martin D.

AU - Wain, Louise V.

PY - 2019/3

Y1 - 2019/3

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85062074587

U2 - 10.1038/s41588-018-0321-7

DO - 10.1038/s41588-018-0321-7

M3 - Article

C2 - 30804560

SN - 1061-4036

VL - 51

SP - 481

EP - 493

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

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

Abstract

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Author Correction: New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries (Nature Genetics, (2019), 10.1038/s41588-018-0321-7)

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

Smith, Blair, FRSE MD MEd FRCGP FHEA FFPMRCA FRCP Edin

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Research output

Author Correction: New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries (Nature Genetics, (2019), 10.1038/s41588-018-0321-7)

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

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Smith, Blair, FRSE MD MEd FRCGP FHEA FFPMRCA FRCP Edin

Cite this