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

Sakornsakolpat, P; Prokopenko, D; Lamontagne, M; Reeve, NF; Guyatt, AL; Jackson, VE; Shrine, N; ... International COPD Genetics Consortium; + view all (2019) Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell type and phenotype associations. Nature Genetics , 51 pp. 494-505. 10.1038/s41588-018-0342-2. Green open access

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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.

Type: Article
Title: Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell type and phenotype associations
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41588-018-0342-2
Publisher version: https://doi.org/10.1038/s41588-018-0342-2
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > VP: Health
URI: https://discovery.ucl.ac.uk/id/eprint/10060757
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