Faculty, Staff and Student Publications

Publication Date

3-1-2023

Journal

Nature Genetics

DOI

10.1038/s41588-023-01314-0

PMID

36914875

PMCID

PMC10011137

PubMedCentral® Posted Date

3-13-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.

Keywords

Humans, Lung, Genome-Wide Association Study, Genetic Predisposition to Disease, Pulmonary Disease, Chronic Obstructive, Smoking, Polymorphism, Single Nucleotide

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.