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; Jørgen 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

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 BartzSusan 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, Jørgen 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,

Research output: Contribution to journal › Article › Academic › 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.

Original language	English
Pages (from-to)	426–432
Number of pages	7
Journal	Nature Genetics
Volume	49
Issue number	3
DOIs	https://doi.org/10.1038/ng.3752
Publication status	Published - Mar 2017

Keywords

Genome-wide association studies
Respiratory tract diseases

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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. (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{916a13076b634f668b6c0818b0f55653,

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 × 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 = "Genome-wide association studies, Respiratory tract diseases",

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 J{\o}rgen 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 Yeon-Mok Oh and Vonk, {Judith M} and {de Koning}, {Harry J} and Shuguang Leng and Belinsky, {Steven A} and Yohannes Tesfaigzi and Ani Manichaikul and Xin-Qun Wang and Rich, {Stephen S} and Barr, {R Graham} and David Sparrow",

year = "2017",

month = mar,

doi = "10.1038/ng.3752",

language = "English",

volume = "49",

pages = "426–432",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

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, Y-M, Vonk, JM, de Koning, HJ, Leng, S, Belinsky, SA, Tesfaigzi, Y, Manichaikul, A, Wang, X-Q, Rich, SS, Barr, RG, Sparrow, D 2017, 'Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis', Nature Genetics, vol. 49, no. 3, pp. 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, Jørgen

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

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 - Genome-wide association studies

KW - Respiratory tract diseases

U2 - 10.1038/ng.3752

DO - 10.1038/ng.3752

M3 - 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

Keywords

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