Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations

Sakornsakolpat, Phuwanat and Prokopenko, Dmitry and Lamontagne, Maxime and Reeve, Nicola F. and Guyatt, Anna L. and Jackson, Victoria E. and Shrine, Nick and Qiao, Dandi and Bartz, Traci M. and Kim, Deog Kyeom and Lee, Mi Kyeong and Latourelle, Jeanne C. and Li, Xingnan and Morrow, Jarrett D. and Obeidat, Ma'en and Wyss, Annah B. and Bakke, Per and Barr, R. Graham and Beaty, Terri H. and Belinsky, Steven A. and Brusselle, Guy G. and Crapo, James D. and de Jong, Kim and DeMeo, Dawn L. and Fingerlin, Tasha E. and Gharib, Sina A. and Gulsvik, Amund and Hall, Ian P. and Hokanson, John E. and Kim, Woo Jin and Lomas, David A. and London, Stephanie J. and Meyers, Deborah A. and O'Connor, George T. and Rennard, Stephen I. and Schwartz, David A. and Sliwinski, Pawel and Sparrow, David and Strachan, David P. and Tal-Singer, Ruth and Tesfaigzi, Yohannes and Vestbo, Jørgen and Vonk, Judith M. and Yim, Jae-Joon and Zhou, Xiaobo and Bossé, Yohan and Manichaikul, Ani and Lahousse, Lies and Silverman, Edwin K. and Boezen, H. Marike and Wain, Louise V. and Tobin, Martin D. and Hobbs, Brian D. and Cho, Michael H. and SpiroMeta Consortium, and International Copd Genetics Consortium, . (2019) Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations. Nature genetics, 51 (3). pp. 494-505.

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Official URL: https://edoc.unibas.ch/69761/

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Abstract

Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10; -8; ; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.

Faculties and Departments:	09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch) 03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch) 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:	Imboden, Medea and Probst Hensch, Nicole
Item Type:	Article, refereed
Article Subtype:	Research Article
Publisher:	Nature Publ
ISSN:	1061-4036
Note:	Publication type according to Uni Basel Research Database: Journal article
Identification Number:	doi: 10.1038/s41588-018-0342-2 pmid: 30804561
Last Modified:	12 Mar 2019 13:12
Deposited On:	12 Mar 2019 13:12

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