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Title: Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell type and phenotype associations
Authors: Sakornsakolpat, P
Prokopenko, D
Lamontagne, M
Reeve, NF
Guyatt, AL
Jackson, VE
Shrine, N
Qiao, D
Bartz, TM
Kim, DK
Lee, MK
Latourelle, JC
Li, X
Morrow, JD
Obeidat, M
Wyss, AB
Bakke, P
Barr, RG
Beaty, TH
Belinsky, SA
Brusselle, GG
Crapo, JD
de Jong, K
DeMeo, DL
Fingerlin, TE
Gharib, SA
Gulsvik, A
Hall, IP
Hokanson, JE
Kim, WJ
Lomas, DA
London, SJ
Meyers, DA
O'Connor, GT
Rennard, SI
Schwartz, DA
Sliwinski, P
Sparrow, D
Strachan, DP
Tal-Singer, R
Tesfaigzi, Y
Vestbo, J
Vonk, JM
Yim, J-J
Zhou, X
Bossé, Y
Manichaikul, A
Lahousse, L
Silverman, EK
Boezen, HM
Wain, LV
Tobin, MD
Hobbs, BD
Cho, MH
SpiroMeta Consortium
International COPD Genetics Consortium
First Published: 25-Feb-2019
Publisher: Nature Research
Citation: Nature Genetics, 2019, 51, pp. 494–505
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.
DOI Link: 10.1038/s41588-018-0342-2
ISSN: 1061-4036
eISSN: 1546-1718
Embargo on file until: 25-Aug-2019
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2019, Springer Nature. Deposited with reference to the publisher’s open access archiving policy. (
Description: The file associated with this record is under embargo until 6 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Appears in Collections:Published Articles, Dept. of Health Sciences

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