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

Hobbs, Brian D., de Jong, Kim, Lamontagne, Maxime, Bossé, Yohan, Shrine, Nick, Artigas, María Soler, Wain, Louise V., Hall, Ian P., Jackson, Victoria E., Wyss, Annah B., London, Stephanie J., North, Kari E., Franceschini, Nora, Strachan, David P., Beaty, Terri H., Hokanson, John E., Crapo, James D., Castaldi, Peter J., Chase, Robert P., Bartz, Traci M., Heckbert, Susan R., Psaty, Bruce M., Gharib, Sina A., Zanen, Pieter, Lammers, Jan W., Oudkerk, Matthijs, Groen, H.J., Locantore, Nicholas, Tal-Singer, Ruth, Rennard, Stephen I., Vestbo, Jørgen, Timens, Wim, Paré, Peter D., Latourelle, Jeanne C., Dupuis, Josée, O'Connor, George T., Wilk, Jemma B., Kim, Woo Jin, Lee, Mi Kyeong, Oh, Yeon-Mok, Vonk, Judith M., de Koning, Harry J., Leng, Shuguang, Belinsky, Steven A., Tesfaigzi, Yohannes, Manichaikul, Ani, Wang, Xin-Qun, Rich, Stephen S., Barr, R. Graham, Sparrow, David, Litonjua, Augusto A., Bakke, Per, Gulsvik, Amund, Lahousse, Lies, Brusselle, Guy G., Stricker, Bruno H., Uitterlinden, André G., Ampleford, Elizabeth J., Bleecker, Eugene R., Woodruff, Prescott G., Meyers, Deborah A., Qiao, Dandi, Lomas, David A., Yim, Jae-Joon, Kim, Deog Kyeom, Hawrylkiewicz, Iwona, Sliwinski, Pawel, Hardin, Megan, Fingerlin, Tasha E., Schwartz, David A., Postma, Dirkje S., MacNee, William, Tobin, Martin D., Silverman, Edwin K., Boezen, H. Marike and Cho, Michael H. (2017) Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis. Nature Genetics, 49 (3). pp. 426-432. ISSN 1546-1718

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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.

Item Type: Article
RIS ID: https://nottingham-repository.worktribe.com/output/847301
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Respiratory Medicine
Identification Number: https://doi.org/10.1038/ng.3752
Depositing User: Hall, Ian
Date Deposited: 21 Jul 2017 09:34
Last Modified: 04 May 2020 18:35
URI: https://eprints.nottingham.ac.uk/id/eprint/44316

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