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Sakornsakolpat, P.* ; Prokopenko, D.* ; Lamontagne, M.* ; Reeve, N.F.* ; Guyatt, A.L.* ; Jackson, V.E.* ; Shrine, N.* ; Qiao, D.* ; Bartz, T.M.* ; Kim, D.K.* ; Lee, M.K.* ; Latourelle, J.C.* ; Li, X.* ; Morrow, J.D.* ; Obeidat, M.* ; Wyss, A.B.* ; Bakke, P.* ; Barr, R.G.* ; Beaty, T.H.* ; Belinsky, S.A.* ; Brusselle, G.G.* ; Crapo, J.D.* ; de Jong, K.* ; DeMeo, D.L.* ; Fingerlin, T.E.* ; Gharib, S.A.* ; Gulsvik, A.* ; Hall, I.P.* ; Hokanson, J.E.* ; Kim, W.J.* ; Lomas, D.A.* ; London, S.J.* ; Meyers, D.A.* ; O’Connor, G.T.* ; Rennard, S.I.* ; Schwartz, D.A.* ; Sliwinski, P.* ; Sparrow, D.B.* ; Strachan, D.P.* ; Tal-Singer, R.* ; Tesfaigzi, Y.* ; Vestbo, J.* ; Vonk, J.M.* ; Yim, J.-J.* ; Zhou, X.* ; Bossé, Y.* ; Manichaikul, A.* ; Lahousse, L.* ; Silverman, E.K.* ; Boezen, H.M.* ; Wain, L.V.* ; Tobin, M.D.* ; Hobbs, B.D.* ; Cho, M.H.* ; SpiroMeta Consortium (Karrasch, S. ; Gieger, C. ; Rawal, R. ; Schulz, H. ; Zeggini, E.)

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

Nat. Genet. 51, 494-505 (2019)
Postprint DOI PMC
Open Access Green
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 x 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Genome-wide Association; Acidic-mammalian-chitinase; Ld Score Regression; Lung-function; Extracellular-matrix; Predominant Emphysema; Connectivity Map; Atopic Asthma; Risk Loci; Gwas
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 51, Issue: 3, Pages: 494-505 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Institute of Translational Genomics (ITG)