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Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.

Original publication

DOI

10.1038/s41588-018-0321-7

Type

Journal article

Journal

Nat Genet

Publication Date

03/2019

Volume

51

Pages

481 - 493

Keywords

Aged, Aged, 80 and over, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Lung, Male, Middle Aged, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, Risk Factors, Smoking