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

Understanding Society Scientific Group

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish
Pages (from-to)481-493
Number of pages13
JournalNature Genetics
Volume51
Issue number3
Early online date25 Feb 2019
DOIs
Publication statusPublished - Mar 2019

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Chronic Obstructive Pulmonary Disease
Lung
Genome-Wide Association Study
Mortality
Pharmaceutical Preparations
Population
Therapeutics

Keywords

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease/genetics
  • Genome-Wide Association Study/methods
  • Humans
  • Lung/physiopathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide/genetics
  • Pulmonary Disease, Chronic Obstructive/genetics
  • Risk Factors
  • Smoking/genetics
  • GWAS
  • VARIANTS
  • LOCI
  • HERITABILITY
  • GENOME-WIDE ASSOCIATION
  • COPD

Cite this

New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. / Understanding Society Scientific Group.

In: Nature Genetics, Vol. 51, No. 3, 03.2019, p. 481-493.

Research output: Contribution to journalArticle

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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.",
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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

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AU - Hansell, Anna L

AU - Hao, Ke

AU - Hoffman, Joshua D

AU - Hokanson, John E

AU - Murray, Alison

AU - Understanding Society Scientific Group

N1 - This research has been conducted using the UK Biobank Resource under applications 648, 4892 and 26041. L. Wain holds a GSK/British Lung Foundation Chair in Respiratory Research. M. Tobin is supported by a Wellcome Trust Investigator Award (WT202849/Z/16/Z). M. Tobin and L. Wain have been supported by the Medical Research Council (MRC) (MR/N011317/1). The research was partially supported by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre; the views expressed are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health. I.H. was partially supported by the NIHR Nottingham Biomedical Research Centre; the views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. This research used the ALICE and SPECTRE High Performance Computing Facilities at the University of Leicester. Additional acknowledgments and funding details for other co-authors and contributing studies (including the SpiroMeta consortium) are in the Supplementary Note. Correction to: Nature Genetics https://doi.org/10.1038/s41588-018-0321-7, published online 25 February 2019.

PY - 2019/3

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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.

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KW - Aged

KW - Aged, 80 and over

KW - Case-Control Studies

KW - Female

KW - Genetic Predisposition to Disease/genetics

KW - Genome-Wide Association Study/methods

KW - Humans

KW - Lung/physiopathology

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide/genetics

KW - Pulmonary Disease, Chronic Obstructive/genetics

KW - Risk Factors

KW - Smoking/genetics

KW - GWAS

KW - VARIANTS

KW - LOCI

KW - HERITABILITY

KW - GENOME-WIDE ASSOCIATION

KW - COPD

UR - https://doi.org/10.1038/s41588-019-0438-3

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U2 - 10.1038/s41588-018-0321-7

DO - 10.1038/s41588-018-0321-7

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VL - 51

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JO - Nature Genetics

JF - Nature Genetics

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