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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.

Original publication

DOI

10.1038/s41588-018-0342-2

Type

Journal article

Journal

Nature genetics

Publication Date

03/2019

Volume

51

Pages

494 - 505

Addresses

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Keywords

SpiroMeta Consortium, International COPD Genetics Consortium, Lung, Humans, Asthma, Pulmonary Fibrosis, Pulmonary Disease, Chronic Obstructive, Genetic Predisposition to Disease, Case-Control Studies, Smoking, Gene Expression, Phenotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Female, Male, Genome-Wide Association Study, Genetic Loci