Header

UZH-Logo

Maintenance Infos

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


Sakornsakolpat, Phuwanat; Prokopenko, Dmitry; Lamontagne, Maxime; et al; Puhan, Milo (2019). Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations. Nature Genetics, 51(3):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; 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.

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; 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.

Statistics

Citations

Dimensions.ai Metrics
35 citations in Web of Science®
33 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

23 downloads since deposited on 17 Oct 2019
23 downloads since 12 months
Detailed statistics

Additional indexing

Contributors:SpiroMeta Consortium, International COPD Genetics Consortium
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Genetics
Language:English
Date:March 2019
Deposited On:17 Oct 2019 07:10
Last Modified:29 Jul 2020 11:28
Publisher:Nature Publishing Group
ISSN:1061-4036
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41588-018-0342-2
PubMed ID:30804561

Download

Green Open Access

Download PDF  'Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations'.
Preview
Content: Published Version
Filetype: PDF
Size: 1MB
View at publisher