Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis

Brian D. Hobbs; Kim De Jong; Maxime Lamontagne; Yohan Bossé; Nick Shrine; María Soler Artigas; Louise V. Wain; Ian P. Hall; Victoria E. Jackson; Annah B. Wyss; Stephanie J. London; Kari E. North; Nora Franceschini; David P. Strachan; Terri H. Beaty; John E. Hokanson; James D. Crapo; Peter J. Castaldi; Robert P. Chase; Traci M. Bartz; Susan R. Heckbert; Bruce M. Psaty; Sina A. Gharib; Pieter Zanen; Jan W. Lammers; Matthijs Oudkerk; H. J. Groen; Nicholas Locantore; Ruth Tal-Singer; Stephen I. Rennard; Jorgen Vestbo; Wim Timens; Peter D. Paré; Jeanne C. Latourelle; Josée Dupuis; George T. O'Connor; Jemma B. Wilk; Woo Jin Kim; Mi Kyeong Lee; Yeon Mok Oh; Judith M. Vonk; Harry J. De Koning; Shuguang Leng; Steven A. Belinsky; Yohannes Tesfaigzi; Ani Manichaikul; Xin Qun Wang; Stephen S. Rich; R. Graham Barr; David Sparrow; COPDGene Investigators; ECLIPSE Investigators

doi:10.1038/ng.3752

Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis

Brian D. Hobbs
, Kim De Jong
, Maxime Lamontagne
, Yohan Bossé
, Nick Shrine
, María Soler Artigas
, Louise V. Wain
, Ian P. Hall
, Victoria E. Jackson
, Annah B. Wyss
, Stephanie J. London
, Kari E. North
, Nora Franceschini
, David P. Strachan
, Terri H. Beaty
, John E. Hokanson
, James D. Crapo
, Peter J. Castaldi
, Robert P. Chase
, Traci M. Bartz

Susan R. Heckbert, Bruce M. Psaty, Sina A. Gharib, Pieter Zanen, Jan W. Lammers, Matthijs Oudkerk, H. J. Groen, Nicholas Locantore, Ruth Tal-Singer, Stephen I. Rennard, Jorgen Vestbo, Wim Timens, Peter D. Paré, Jeanne C. Latourelle, Josée Dupuis, George T. O'Connor, Jemma B. Wilk, Woo Jin Kim, Mi Kyeong Lee, Yeon Mok Oh, Judith M. Vonk, Harry J. De Koning, Shuguang Leng, Steven A. Belinsky, Yohannes Tesfaigzi, Ani Manichaikul, Xin Qun Wang, Stephen S. Rich, R. Graham Barr, David Sparrow, COPDGene Investigators, ECLIPSE Investigators

The University of Manchester

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P <5 × 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	49
Udgave nummer	3
Sider (fra-til)	426-432
Antal sider	7
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.3752
Status	Udgivet - mar. 2017
Udgivet eksternt	Ja

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10.1038/ng.3752

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Hobbs, B. D., De Jong, K., Lamontagne, M., Bossé, Y., Shrine, N., Artigas, M. S., Wain, L. V., Hall, I. P., Jackson, V. E., Wyss, A. B., London, S. J., North, K. E., Franceschini, N., Strachan, D. P., Beaty, T. H., Hokanson, J. E., Crapo, J. D., Castaldi, P. J., Chase, R. P., ... ECLIPSE Investigators (2017). Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis. Nature Genetics, 49(3), 426-432. https://doi.org/10.1038/ng.3752

@article{4d7f3134f54c43ab8c62550e9474bbeb,

title = "Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis",

abstract = "Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P <5 {\texttimes} 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.",

keywords = "Adult, Aged, Aged, 80 and over, Alleles, Asthma/genetics, Female, Genetic Loci/genetics, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study/methods, Humans, Lung/physiology, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide/genetics, Pulmonary Disease, Chronic Obstructive/genetics, Pulmonary Fibrosis/genetics, Risk Factors, Smoking/genetics",

author = "Hobbs, \{Brian D.\} and \{De Jong\}, Kim and Maxime Lamontagne and Yohan Boss{\'e} and Nick Shrine and Artigas, \{Mar{\'i}a Soler\} and Wain, \{Louise V.\} and Hall, \{Ian P.\} and Jackson, \{Victoria E.\} and Wyss, \{Annah B.\} and London, \{Stephanie J.\} and North, \{Kari E.\} and Nora Franceschini and Strachan, \{David P.\} and Beaty, \{Terri H.\} and Hokanson, \{John E.\} and Crapo, \{James D.\} and Castaldi, \{Peter J.\} and Chase, \{Robert P.\} and Bartz, \{Traci M.\} and Heckbert, \{Susan R.\} and Psaty, \{Bruce M.\} and Gharib, \{Sina A.\} and Pieter Zanen and Lammers, \{Jan W.\} and Matthijs Oudkerk and Groen, \{H. J.\} and Nicholas Locantore and Ruth Tal-Singer and Rennard, \{Stephen I.\} and Jorgen Vestbo and Wim Timens and Par{\'e}, \{Peter D.\} and Latourelle, \{Jeanne C.\} and Jos{\'e}e Dupuis and O'Connor, \{George T.\} and Wilk, \{Jemma B.\} and Kim, \{Woo Jin\} and Lee, \{Mi Kyeong\} and Oh, \{Yeon Mok\} and Vonk, \{Judith M.\} and \{De Koning\}, \{Harry J.\} and Shuguang Leng and Belinsky, \{Steven A.\} and Yohannes Tesfaigzi and Ani Manichaikul and Wang, \{Xin Qun\} and Rich, \{Stephen S.\} and Barr, \{R. Graham\} and David Sparrow and \{COPDGene Investigators\} and \{ECLIPSE Investigators\}",

year = "2017",

month = mar,

doi = "10.1038/ng.3752",

language = "English",

volume = "49",

pages = "426--432",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "3",

}

Hobbs, BD, De Jong, K, Lamontagne, M, Bossé, Y, Shrine, N, Artigas, MS, Wain, LV, Hall, IP, Jackson, VE, Wyss, AB, London, SJ, North, KE, Franceschini, N, Strachan, DP, Beaty, TH, Hokanson, JE, Crapo, JD, Castaldi, PJ, Chase, RP, Bartz, TM, Heckbert, SR, Psaty, BM, Gharib, SA, Zanen, P, Lammers, JW, Oudkerk, M, Groen, HJ, Locantore, N, Tal-Singer, R, Rennard, SI, Vestbo, J, Timens, W, Paré, PD, Latourelle, JC, Dupuis, J, O'Connor, GT, Wilk, JB, Kim, WJ, Lee, MK, Oh, YM, Vonk, JM, De Koning, HJ, Leng, S, Belinsky, SA, Tesfaigzi, Y, Manichaikul, A, Wang, XQ, Rich, SS, Barr, RG, Sparrow, D, COPDGene Investigators & ECLIPSE Investigators 2017, 'Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis', Nature Genetics, bind 49, nr. 3, s. 426-432. https://doi.org/10.1038/ng.3752

TY - JOUR

T1 - Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis

AU - Hobbs, Brian D.

AU - De Jong, Kim

AU - Lamontagne, Maxime

AU - Bossé, Yohan

AU - Shrine, Nick

AU - Artigas, María Soler

AU - Wain, Louise V.

AU - Hall, Ian P.

AU - Jackson, Victoria E.

AU - Wyss, Annah B.

AU - London, Stephanie J.

AU - North, Kari E.

AU - Franceschini, Nora

AU - Strachan, David P.

AU - Beaty, Terri H.

AU - Hokanson, John E.

AU - Crapo, James D.

AU - Castaldi, Peter J.

AU - Chase, Robert P.

AU - Bartz, Traci M.

AU - Heckbert, Susan R.

AU - Psaty, Bruce M.

AU - Gharib, Sina A.

AU - Zanen, Pieter

AU - Lammers, Jan W.

AU - Oudkerk, Matthijs

AU - Groen, H. J.

AU - Locantore, Nicholas

AU - Tal-Singer, Ruth

AU - Rennard, Stephen I.

AU - Vestbo, Jorgen

AU - Timens, Wim

AU - Paré, Peter D.

AU - Latourelle, Jeanne C.

AU - Dupuis, Josée

AU - O'Connor, George T.

AU - Wilk, Jemma B.

AU - Kim, Woo Jin

AU - Lee, Mi Kyeong

AU - Oh, Yeon Mok

AU - Vonk, Judith M.

AU - De Koning, Harry J.

AU - Leng, Shuguang

AU - Belinsky, Steven A.

AU - Tesfaigzi, Yohannes

AU - Manichaikul, Ani

AU - Wang, Xin Qun

AU - Rich, Stephen S.

AU - Barr, R. Graham

AU - Sparrow, David

AU - COPDGene Investigators

AU - ECLIPSE Investigators

PY - 2017/3

Y1 - 2017/3

N2 - Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P <5 × 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

AB - Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P <5 × 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - Asthma/genetics

KW - Female

KW - Genetic Loci/genetics

KW - Genetic Predisposition to Disease/genetics

KW - Genome-Wide Association Study/methods

KW - Humans

KW - Lung/physiology

KW - Male

KW - Middle Aged

KW - Phenotype

KW - Polymorphism, Single Nucleotide/genetics

KW - Pulmonary Disease, Chronic Obstructive/genetics

KW - Pulmonary Fibrosis/genetics

KW - Risk Factors

KW - Smoking/genetics

U2 - 10.1038/ng.3752

DO - 10.1038/ng.3752

M3 - Journal article

C2 - 28166215

SN - 1061-4036

VL - 49

SP - 426

EP - 432

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis

Abstract

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