Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations

SpiroMeta consortium, International COPD Genetics Consortium, Understanding Society Scientific Group

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10 −8 ; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.

Original languageEnglish
Pages (from-to)494-505
Number of pages12
JournalNature Genetics
Volume51
Issue number3
DOIs
Publication statusPublished - 25 Feb 2019

Fingerprint

Chronic Obstructive Pulmonary Disease
Phenotype
Lung
Genetic Loci
Genetic Heterogeneity
Pulmonary Fibrosis
Genome-Wide Association Study
Gene Expression Regulation
Genetic Predisposition to Disease
Smooth Muscle
Comorbidity
Asthma
Mortality
Population

Cite this

SpiroMeta consortium, International COPD Genetics Consortium, & Understanding Society Scientific Group (2019). Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations. Nature Genetics, 51(3), 494-505. https://doi.org/10.1038/s41588-018-0342-2
SpiroMeta consortium ; International COPD Genetics Consortium ; Understanding Society Scientific Group. / Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations. In: Nature Genetics. 2019 ; Vol. 51, No. 3. pp. 494-505.
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abstract = "Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10 −8 ; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.",
author = "{SpiroMeta consortium} and {International COPD Genetics Consortium} and {Understanding Society Scientific Group} and Phuwanat Sakornsakolpat and Dmitry Prokopenko and Maxime Lamontagne and Reeve, {Nicola F.} and Guyatt, {Anna L.} and Jackson, {Victoria E.} and Nick Shrine and Dandi Qiao and Bartz, {Traci M.} and Kim, {Deog Kyeom} and Lee, {Mi Kyeong} and Latourelle, {Jeanne C.} and Xingnan Li and Morrow, {Jarrett D.} and Ma’en Obeidat and Wyss, {Annah B.} and Per Bakke and Barr, {R. Graham} and Beaty, {Terri H.} and Belinsky, {Steven A.} and Brusselle, {Guy G.} and Crapo, {James D.} and {de Jong}, Kim and DeMeo, {Dawn L.} and Fingerlin, {Tasha E.} and Gharib, {Sina A.} and Amund Gulsvik and Hall, {Ian P.} and Hokanson, {John E.} and Kim, {Woo Jin} and Lomas, {David A.} and London, {Stephanie J.} and Meyers, {Deborah A.} and O’Connor, {George T.} and Rennard, {Stephen I.} and Schwartz, {David A.} and Pawel Sliwinski and David Sparrow and Strachan, {David P.} and Ruth Tal-Singer and Yohannes Tesfaigzi and J{\o}rgen Vestbo and Vonk, {Judith M.} and Yim, {Jae Joon} and Xiaobo Zhou and Yohan Boss{\'e} and Ani Manichaikul and Lies Lahousse and Silverman, {Edwin K.} and Boezen, {H. Marike} and Wain, {Louise V.} and Tobin, {Martin D.} and Hobbs, {Brian D.} and Cho, {Michael H.} and Nick Shrine and Guyatt, {Anna L.} and Chiara Batini and Zhao, {Jing Hua} and Matthias Wielscher and Stefan Weiss and Kentistou, {Katherine A.} and Cook, {James P.} 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 Ralf Ewert and Christian Gieger and Georg Homuth and Joshi, {Peter K.} and Claudia Langenberg and Lars Lind and Jian’an Luan and Anubha Mahajan and Alison Murray and Porteous, {David J.} and Rajesh Rawal and Smith, {Blair H.} and Timmers, {Paul R.H.J.} and Raitakari, {Olli T.} and Mika K{\"a}h{\"o}nen and Ozren Polasek and Ulf Gyllensten and Igor Rudan and Deary, {Ian J.} and Probst-Hensch, {Nicole M.} and Holger Schulz and James, {Alan L.} and Wilson, {James F.} and Beate Stubbe and Eleftheria Zeggini and Jarvelin, {Marjo Riitta} and Nick Wareham and Caroline Hayward and Morris, {Andrew P.} and Strachan, {David P.} and Hall, {Ian P.} and Tobin, {Martin D.} and Wain, {Louise V.} and Alvar Agusti and Wayne Anderson and Nawar Bakerly and Per Bakke and Robert Bals and Barnes, {Kathleen C.} and Barr, {R. Graham} and Beaty, {Terri H.} and Bleecker, {Eugene R.} and Boezen, {H. Marike} and Yohan Boss{\'e} and Russell Bowler and Christopher Brightling and {de Bruijne}, Marleen and Castaldi, {Peter J.} and Bartolome Celli and Cho, {Michael H.} and Coxson, {Harvey O.} and Crapo, {James D.} and Ron Crystal and {de Jong}, Pim and Asger Dirksen and Jennifer Dy and Marilyn Foreman and Judith Garcia-Aymerich and Pierre Gevenois and Soumitra Ghosh and Hester Gietema and Amund Gulsvik and Hall, {Ian P.} and Nadia Hansel and Hersh, {Craig P.} and Hobbs, {Brian D.} and Eric Hoffman and Noor Kalsheker and Kauczor, {Hans Ulrich} and Kim, {Woo Jin} and Kim, {Deog Kyeom} and Tarja Laitinen and Diether Lambrechts and Lee, {Sang Do} and Litonjua, {Augusto A.} and Lomas, {David A.} and London, {Stephanie J.} and Loth, {Daan W.} and Lutz, {Sharon M.} and David Lynch and William MacNee and McDonald, {Merry Lynn} and Meyers, {Deborah A.} and Newell, {John D.} and Nordestgaard, {Borge G.} and O’Connor, {George T.} and Ma’en Obeidat and Oh, {Yeon Mok} and Par{\'e}, {Peter D.} and Massimo Pistolesi and Postma, {Dirkje S.} and Milo Puhan and Elizabeth Regan and Rich, {Stephen S.} and Seo, {Joon Beom} and Andrea Short and Silverman, {Edwin K.} and David Sparrow and Berend Stoel and Strachan, {David P.} and Nicola Sverzellati and Ruth Tal-Singer and {ter Riet}, Gerben and Yohannes Tesfaigzi and Tobin, {Martin D.} and {Van Beek}, {Edwin J.R.} and {van Ginneken}, Bram and J{\o}rgen Vestbo and Vogelmeier, {Claus F.} and Wain, {Louise V.} and Adam Wanner and George Washko and Els Wauters and Wouters, {Emiel F.M.} and Young, {Robert P.} and Loems Zeigler-Heitbrock",
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SpiroMeta consortium, International COPD Genetics Consortium & Understanding Society Scientific Group 2019, 'Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations' Nature Genetics, vol. 51, no. 3, pp. 494-505. https://doi.org/10.1038/s41588-018-0342-2

Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations. / SpiroMeta consortium; International COPD Genetics Consortium; Understanding Society Scientific Group.

In: Nature Genetics, Vol. 51, No. 3, 25.02.2019, p. 494-505.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations

AU - SpiroMeta consortium

AU - International COPD Genetics Consortium

AU - Understanding Society Scientific Group

AU - Sakornsakolpat, Phuwanat

AU - Prokopenko, Dmitry

AU - Lamontagne, Maxime

AU - Reeve, Nicola F.

AU - Guyatt, Anna L.

AU - Jackson, Victoria E.

AU - Shrine, Nick

AU - Qiao, Dandi

AU - Bartz, Traci M.

AU - Kim, Deog Kyeom

AU - Lee, Mi Kyeong

AU - Latourelle, Jeanne C.

AU - Li, Xingnan

AU - Morrow, Jarrett D.

AU - Obeidat, Ma’en

AU - Wyss, Annah B.

AU - Bakke, Per

AU - Barr, R. Graham

AU - Beaty, Terri H.

AU - Belinsky, Steven A.

AU - Brusselle, Guy G.

AU - Crapo, James D.

AU - de Jong, Kim

AU - DeMeo, Dawn L.

AU - Fingerlin, Tasha E.

AU - Gharib, Sina A.

AU - Gulsvik, Amund

AU - Hall, Ian P.

AU - Hokanson, John E.

AU - Kim, Woo Jin

AU - Lomas, David A.

AU - London, Stephanie J.

AU - Meyers, Deborah A.

AU - O’Connor, George T.

AU - Rennard, Stephen I.

AU - Schwartz, David A.

AU - Sliwinski, Pawel

AU - Sparrow, David

AU - Strachan, David P.

AU - Tal-Singer, Ruth

AU - Tesfaigzi, Yohannes

AU - Vestbo, Jørgen

AU - Vonk, Judith M.

AU - Yim, Jae Joon

AU - Zhou, Xiaobo

AU - Bossé, Yohan

AU - Manichaikul, Ani

AU - Lahousse, Lies

AU - Silverman, Edwin K.

AU - Boezen, H. Marike

AU - Wain, Louise V.

AU - Tobin, Martin D.

AU - Hobbs, Brian D.

AU - Cho, Michael H.

AU - Shrine, Nick

AU - Guyatt, Anna L.

AU - Batini, Chiara

AU - Zhao, Jing Hua

AU - Wielscher, Matthias

AU - Weiss, Stefan

AU - Kentistou, Katherine A.

AU - Cook, James P.

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 - Ewert, Ralf

AU - Gieger, Christian

AU - Homuth, Georg

AU - Joshi, Peter K.

AU - Langenberg, Claudia

AU - Lind, Lars

AU - Luan, Jian’an

AU - Mahajan, Anubha

AU - Murray, Alison

AU - Porteous, David J.

AU - Rawal, Rajesh

AU - Smith, Blair H.

AU - Timmers, Paul R.H.J.

AU - Raitakari, Olli T.

AU - Kähönen, Mika

AU - Polasek, Ozren

AU - Gyllensten, Ulf

AU - Rudan, Igor

AU - Deary, Ian J.

AU - Probst-Hensch, Nicole M.

AU - Schulz, Holger

AU - James, Alan L.

AU - Wilson, James F.

AU - Stubbe, Beate

AU - Zeggini, Eleftheria

AU - Jarvelin, Marjo Riitta

AU - Wareham, Nick

AU - Hayward, Caroline

AU - Morris, Andrew P.

AU - Strachan, David P.

AU - Hall, Ian P.

AU - Tobin, Martin D.

AU - Wain, Louise V.

AU - Agusti, Alvar

AU - Anderson, Wayne

AU - Bakerly, Nawar

AU - Bakke, Per

AU - Bals, Robert

AU - Barnes, Kathleen C.

AU - Barr, R. Graham

AU - Beaty, Terri H.

AU - Bleecker, Eugene R.

AU - Boezen, H. Marike

AU - Bossé, Yohan

AU - Bowler, Russell

AU - Brightling, Christopher

AU - de Bruijne, Marleen

AU - Castaldi, Peter J.

AU - Celli, Bartolome

AU - Cho, Michael H.

AU - Coxson, Harvey O.

AU - Crapo, James D.

AU - Crystal, Ron

AU - de Jong, Pim

AU - Dirksen, Asger

AU - Dy, Jennifer

AU - Foreman, Marilyn

AU - Garcia-Aymerich, Judith

AU - Gevenois, Pierre

AU - Ghosh, Soumitra

AU - Gietema, Hester

AU - Gulsvik, Amund

AU - Hall, Ian P.

AU - Hansel, Nadia

AU - Hersh, Craig P.

AU - Hobbs, Brian D.

AU - Hoffman, Eric

AU - Kalsheker, Noor

AU - Kauczor, Hans Ulrich

AU - Kim, Woo Jin

AU - Kim, Deog Kyeom

AU - Laitinen, Tarja

AU - Lambrechts, Diether

AU - Lee, Sang Do

AU - Litonjua, Augusto A.

AU - Lomas, David A.

AU - London, Stephanie J.

AU - Loth, Daan W.

AU - Lutz, Sharon M.

AU - Lynch, David

AU - MacNee, William

AU - McDonald, Merry Lynn

AU - Meyers, Deborah A.

AU - Newell, John D.

AU - Nordestgaard, Borge G.

AU - O’Connor, George T.

AU - Obeidat, Ma’en

AU - Oh, Yeon Mok

AU - Paré, Peter D.

AU - Pistolesi, Massimo

AU - Postma, Dirkje S.

AU - Puhan, Milo

AU - Regan, Elizabeth

AU - Rich, Stephen S.

AU - Seo, Joon Beom

AU - Short, Andrea

AU - Silverman, Edwin K.

AU - Sparrow, David

AU - Stoel, Berend

AU - Strachan, David P.

AU - Sverzellati, Nicola

AU - Tal-Singer, Ruth

AU - ter Riet, Gerben

AU - Tesfaigzi, Yohannes

AU - Tobin, Martin D.

AU - Van Beek, Edwin J.R.

AU - van Ginneken, Bram

AU - Vestbo, Jørgen

AU - Vogelmeier, Claus F.

AU - Wain, Louise V.

AU - Wanner, Adam

AU - Washko, George

AU - Wauters, Els

AU - Wouters, Emiel F.M.

AU - Young, Robert P.

AU - Zeigler-Heitbrock, Loems

PY - 2019/2/25

Y1 - 2019/2/25

N2 - Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10 −8 ; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.

AB - Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10 −8 ; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.

UR - http://www.scopus.com/inward/record.url?scp=85062145797&partnerID=8YFLogxK

U2 - 10.1038/s41588-018-0342-2

DO - 10.1038/s41588-018-0342-2

M3 - Article

VL - 51

SP - 494

EP - 505

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 3

ER -

SpiroMeta consortium, International COPD Genetics Consortium, Understanding Society Scientific Group. Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations. Nature Genetics. 2019 Feb 25;51(3):494-505. https://doi.org/10.1038/s41588-018-0342-2