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

被引：284

作者：

Hobbs, Brian D. ^{[1
,2
]}

de Jong, Kim ^{[3
,4
]}

Lamontagne, Maxime ^{[5
]}

Bosse, Yohan ^{[5
,6
]}

Shrine, Nick ^{[7
]}

Artigas, Maria Soler ^{[7
]}

Wain, Louise V. ^{[7
]}

Hall, Ian P. ^{[8
]}

Jackson, Victoria E. ^{[7
]}

Wyss, Annah B. ^{[9
]}

London, Stephanie J. ^{[9
]}

North, Kari E. ^{[10
]}

Franceschini, Nora ^{[10
]}

Strachan, David P. ^{[11
]}

Beaty, Terri H. ^{[12
]}

Hokanson, John E. ^{[13
]}

Crapo, James D. ^{[14
]}

Castaldi, Peter J. ^{[1
,15
]}

Chase, Robert P. ^{[1
]}

Bartz, Traci M. ^{[16
,17
,18
]}

Heckbert, Susan R. ^{[16
,19
,20
]}

Psaty, Bruce M. ^{[16
,17
,19
,20
,21
]}

Gharib, Sina A. ^{[22
]}

Zanen, Pieter ^{[23
]}

Lammers, Jan W. ^{[23
]}

Oudkerk, Matthijs ^{[24
]}

Groen, H. J. ^{[25
]}

Locantore, Nicholas ^{[26
]}

Tal-Singer, Ruth ^{[26
]}

Rennard, Stephen I. ^{[27
,28
]}

Vestbo, Jurgen ^{[29
]}

Timens, Wim ^{[30
]}

Pare, Peter D. ^{[31
,32
]}

Latourelle, Jeanne C. ^{[33
]}

Dupuis, Josee ^{[34
,35
]}

O'Connor, George T. ^{[35
,36
]}

Wilk, Jemma B. ^{[35
]}

Kim, Woo Jin ^{[37
,38
]}

Lee, Mi Kyeong ^{[37
,38
]}

Oh, Yeon-Mok ^{[39
,40
]}

Vonk, Judith M. ^{[3
,4
]}

de Koning, Harry J. ^{[41
]}

Leng, Shuguang ^{[42
]}

Belinsky, Steven A. ^{[42
]}

Tesfaigzi, Yohannes ^{[42
]}

Manichaikul, Ani ^{[43
,44
]}

Wang, Xin-Qun ^{[44
]}

Rich, Stephen S. ^{[43
,44
]}

Barr, R. Graham ^{[45
,46
]}

Sparrow, David ^{[47
,48
]}

机构：

[1] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA

[3] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands

[4] Univ Groningen, Univ Med Ctr Groningen, GRIAC, Groningen, Netherlands

[5] Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada

[6] Univ Laval, Dept Mol Med, Quebec City, PQ, Canada

[7] Univ Leicester, Dept Hlth Sci, Genet Epidemiol Grp, Leicester, Leics, England

[8] Univ Nottingham, Queens Med Ctr, Div Resp Med, Nottingham, England

[9] US Dept Hlth & Human Serv, Epidemiol Branch, NIEHS, US Natl Inst Hlth, Res Triangle Pk, NC USA

[10] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA

[11] St Georges Univ London, Populat Hlth Res Inst, London, England

[12] Johns Hopkins Univ Bloomberg Sch Publ Hlth, Baltimore, MD USA

[13] Univ Colorado, Dept Epidemiol, Anschutz Med Campus, Aurora, CO USA

[14] Natl Jewish Hlth, Dept Med, Div Pulm & Crit Care Med, Denver, CO USA

[15] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA

[16] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[17] Univ Washington, Dept Med, Seattle, WA USA

[18] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[19] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[20] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA

[21] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA

[22] Univ Washington, Dept Med, UW Med Sleep Ctr, Computat Med Core,Ctr Lung Biol, Seattle, WA USA

[23] Univ Utrecht, Univ Med Ctr Utrecht, Dept Pulmonol, Utrecht, Netherlands

[24] Univ Groningen, Univ Med Ctr Groningen, Ctr Med Imaging, Groningen, Netherlands

[25] Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol, Groningen, Netherlands

[26] GlaxoSmithKline Res & Dev Ltd, King Of Prussia, PA USA

[27] Univ Nebraska Med Ctr, Dept Internal Med, Pulm Crit Care Sleep & Allergy Div, Omaha, NE USA

[28] AstraZeneca, Clin Discovery Unit, Cambridge, England

[29] Univ Manchester, Sch Biol Sci, Manchester, Lancs, England

[30] Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Dept Pathol & Med Biol, Groningen, Netherlands

[31] Univ British Columbia, Ctr Heart Lung Innovat, Vancouver, BC, Canada

[32] St Pauls Hosp, Inst Heart & Lung Hlth, Vancouver, BC, Canada

[33] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[34] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[35] NHLBI, Framingham Heart Study, Framingham, MA USA

[36] Boston Univ, Sch Med, Dept Med, Pulm Ctr, Boston, MA 02118 USA

[37] Kangwon Natl Univ, Sch Med, Dept Internal Med, Chunchon, South Korea

[38] Kangwon Natl Univ, Sch Med, Ctr Environm Hlth, Chunchon, South Korea

[39] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pulm & Crit Care Med, Seoul, South Korea

[40] Univ Ulsan, Coll Med, Asan Med Ctr, Clin Res Ctr Chron Obstruct Airway Dis, Seoul, South Korea

[41] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands

[42] Lovelace Resp Res Inst, Albuquerque, NM USA

[43] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA

[44] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA

[45] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY USA

[46] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA

[47] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA

[48] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA

[49] Univ Bergen, Dept Clin Sci, Bergen, Norway

[50] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

来源：

NATURE GENETICS | 2017年 / 49卷 / 03期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; SURFACTANT PROTEIN-D; COMPLEX TRAITS; I INTERFERON; VARIANTS; SUSCEPTIBILITY; NLRX1; COPD; MICROTUBULES; DESMOPLAKIN;

D O I：

10.1038/ng.3752

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide(1). We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 x 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(2-7), while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis(8,9) (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(10). 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.

引用

页码：426 / 432

页数：7

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← 1 2 3 4 5 6 →

共 53 条

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Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation [J].

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Wain, Louise V. ;

Miller, Suzanne ;

Kheirallah, Abdul Kader ;

Huffman, Jennifer E. ;

Ntalla, Ioanna ;

Shrine, Nick ;

Obeidat, Ma'en ;

Trochet, Holly ;

McArdle, Wendy L. ;

Alves, Alexessander Couto ;

Hui, Jennie ;

Zhao, Jing Hua ;

Joshi, Peter K. ;

Teumer, Alexander ;

Albrecht, Eva ;

Imboden, Medea ;

Rawal, Rajesh ;

Lopez, Lorna M. ;

Marten, Jonathan ;

Enroth, Stefan ;

Surakka, Ida ;

Polasek, Ozren ;

Lyytikainen, Leo-Pekka ;

Granell, Raquel ;

Hysi, Pirro G. ;

Flexeder, Claudia ;

Mahajan, Anubha ;

Beilby, John ;

Bosse, Yohan ;

Brandsma, Corry-Anke ;

Campbell, Harry ;

Gieger, Christian ;

Glaeser, Sven ;

Gonzalez, Juan R. ;

Grallert, Harald ;

Hammond, Chris J. ;

Harris, Sarah E. ;

Hartikainen, Anna-Liisa ;

Heliovaara, Markku ;

Henderson, John ;

Hocking, Lynne ;

Horikoshi, Momoko ;

Hutri-Kahonen, Nina ;

Ingelsson, Erik ;

Johansson, Asa ;

Kemp, John P. ;

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Lind, Lars .

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An atlas of genetic correlations across human diseases and traits [J].

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Cho, Michael H. ;

McDonald, Merry-Lynn N. ;

Zhou, Xiaobo ;

Mattheisen, Manuel ;

Castaldi, Peter J. ;

Hersh, Craig P. ;

DeMeo, Dawn L. ;

Sylvia, Jody S. ;

Ziniti, John ;

Laird, Nan M. ;

Lange, Christoph ;

Litonjua, Augusto A. ;

Sparrow, David ;

Casaburi, Richard ;

Barr, R. Graham ;

Regan, Elizabeth A. ;

Make, Barry J. ;

Hokanson, John E. ;

Lutz, Sharon ;

Dudenkov, Tanda Murray ;

Farzadegan, Homayoon ;

Hetmanski, Jacqueline B. ;

Tal-Singer, Ruth ;

Lomas, David A. ;

Bakke, Per ;

Gulsvik, Amund ;

Crapo, James D. ;

Silverman, Edwin K. ;

Beaty, Terri H. .

LANCET RESPIRATORY MEDICINE, 2014, 2 (03) :214-225

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A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13 [J].

Cho, Michael H. ;

Castaldi, Peter J. ;

Wan, Emily S. ;

Siedlinski, Mateusz ;

Hersh, Craig P. ;

Demeo, Dawn L. ;

Himes, Blanca E. ;

Sylvia, Jody S. ;

Klanderman, Barbara J. ;

Ziniti, John P. ;

Lange, Christoph ;

Litonjua, Augusto A. ;

Sparrow, David ;

Regan, Elizabeth A. ;

Make, Barry J. ;

Hokanson, John E. ;

Murray, Tanda ;

Hetmanski, Jacqueline B. ;

Pillai, Sreekumar G. ;

Kong, Xiangyang ;

Anderson, Wayne H. ;

Tal-Singer, Ruth ;

Lomas, David A. ;

Coxson, Harvey O. ;

Edwards, Lisa D. ;

MacNee, William ;

Vestbo, Jorgen ;

Yates, Julie C. ;

Agusti, Alvar ;

Calverley, Peter M. A. ;

Celli, Bartolome ;

Crim, Courtney ;

Rennard, Stephen ;

Wouters, Emiel ;

Bakke, Per ;

Gulsvik, Amund ;

Crapo, James D. ;

Beaty, Terri H. ;

Silverman, Edwin K. .

HUMAN MOLECULAR GENETICS, 2012, 21 (04) :947-957

[6]

Variants in FAM13A are associated with chronic obstructive pulmonary disease [J].

Cho, Michael H. ;

Boutaoui, Nadia ;

Klanderman, Barbara J. ;

Sylvia, Jody S. ;

Ziniti, John P. ;

Hersh, Craig P. ;

DeMeo, Dawn L. ;

Hunninghake, Gary M. ;

Litonjua, Augusto A. ;

Sparrow, David ;

Lange, Christoph ;

Won, Sungho ;

Murphy, James R. ;

Beaty, Terri H. ;

Regan, Elizabeth A. ;

Make, Barry J. ;

Hokanson, John E. ;

Crapo, James D. ;

Kong, Xiangyang ;

Anderson, Wayne H. ;

Tal-Singer, Ruth ;

Lomas, David A. ;

Bakke, Per ;

Gulsvik, Amund ;

Pillai, Sreekumar G. ;

Silverman, Edwin K. .

NATURE GENETICS, 2010, 42 (03) :200-202

[7]

Leveraging Multi-ethnic Evidence for Mapping Complex Traits in Minority Populations: An Empirical Bayes Approach [J].

Coram, Marc A. ;

Candille, Sophie I. ;

Duan, Qing ;

Chan, Kei Hang K. ;

Li, Yun ;

Kooperberg, Charles ;

Reiner, Alex P. ;

Tang, Hua .

AMERICAN JOURNAL OF HUMAN GENETICS, 2015, 96 (05) :740-752

[8]

Large-scale association analysis identifies new risk loci for coronary artery disease [J].

Deloukas, Panos ;

Kanoni, Stavroula ;

Willenborg, Christina ;

Farrall, Martin ;

Assimes, Themistocles L. ;

Thompson, John R. ;

Ingelsson, Erik ;

Saleheen, Danish ;

Erdmann, Jeanette ;

Goldstein, Benjamin A. ;

Stirrups, Kathleen ;

Koenig, Inke R. ;

Cazier, Jean-Baptiste ;

Johansson, Asa ;

Hall, Alistair S. ;

Lee, Jong-Young ;

Willer, Cristen J. ;

Chambers, John C. ;

Esko, Tonu ;

Folkersen, Lasse ;

Goel, Anuj ;

Grundberg, Elin ;

Havulinna, Aki S. ;

Ho, Weang K. ;

Hopewell, Jemma C. ;

Eriksson, Niclas ;

Kleber, Marcus E. ;

Kristiansson, Kati ;

Lundmark, Per ;

Lyytikainen, Leo-Pekka ;

Rafelt, Suzanne ;

Shungin, Dmitry ;

Strawbridge, Rona J. ;

Thorleifsson, Gudmar ;

Tikkanen, Emmi ;

Van Zuydam, Natalie ;

Voight, Benjamin F. ;

Waite, Lindsay L. ;

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