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Hobbs, Brian D. and de Jong, Kim and Lamontagne, Maxime and Bossé, Yohan and Shrine, Nick and Artigas, María 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 Franceschini, Nora 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 Zanen, Pieter and Lammers, Jan W. and Oudkerk, Matthijs and Groen, H.J. and Locantore, Nicholas and Tal-Singer, Ruth and Rennard, Stephen I. and Vestbo, Jørgen and Timens, Wim and Paré, Peter D. and Latourelle, Jeanne C. and Dupuis, Josée 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 Leng, Shuguang and Belinsky, Steven A. and Tesfaigzi, Yohannes and Manichaikul, Ani and Wang, Xin-Qun and Rich, Stephen S. and Barr, R. Graham and Sparrow, David and Litonjua, Augusto A. and Bakke, Per and Gulsvik, Amund and Lahousse, Lies and Brusselle, Guy G. and Stricker, Bruno H. and Uitterlinden, André G. and Ampleford, Elizabeth J. and Bleecker, Eugene R. and Woodruff, Prescott G. and Meyers, Deborah A. and Qiao, Dandi and Lomas, David A. and Yim, Jae-Joon and Kim, Deog Kyeom and Hawrylkiewicz, Iwona and Sliwinski, Pawel and Hardin, Megan and Fingerlin, Tasha E. and Schwartz, David A. and Postma, Dirkje S. and MacNee, William and Tobin, Martin D. and Silverman, Edwin K. and 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

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.

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