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New genetic signals for lung function highlight pathways and pleiotropy, and chronic obstructive pulmonary disease associations across multiple ancestries

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    Rights statement: This is an Accepted Manuscript of an article published in Nature Genetics on 25.2.2019, available online:https://www.nature.com/articles/s41588-018-0321-7

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Original languageEnglish
Pages (from-to)481–493
JournalNature Genetics
Volume51
Early online date25 Feb 2019
DOIs
Publication statusPublished - 2019

Abstract

Reduced lung function predicts mortality and is key to the diagnosis of 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 patient populations. Furthermore, the combined effect of these variants showed generalisability 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.

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