Journal article
Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 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 588,452 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Corrected version of record, pdf, 3.1MB, Terms of use)
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(Preview, Other, pdf, 657.6KB, Terms of use)
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- Publisher copy:
- 10.1038/s41588-023-01314-0
Authors
Contributors
+ China Kadoorie Biobank Collaborative Group
- Role:
- Contributor
+ Qatar Genome Program Research (QGPR) Consortium
- Role:
- Contributor
- Publisher:
- Springer Nature
- Journal:
- Nature Genetics More from this journal
- Volume:
- 55
- Issue:
- 3
- Pages:
- 410–422
- Publication date:
- 2023-03-13
- Acceptance date:
- 2023-01-25
- DOI:
- EISSN:
-
1546-1718
- ISSN:
-
1061-4036
- Language:
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English
- Keywords:
- Pubs id:
-
1300793
- Local pid:
-
pubs:1300793
- Deposit date:
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2022-11-09
- ARK identifier:
Terms of use
- Copyright holder:
- Shrine et al.
- Copyright date:
- 2023
- Rights statement:
- © The Author(s) 2023, corrected publication 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Notes:
- A correction to this article is available online from Springer Nature at: https://doi.org/10.1038/s41588-023-01531-7
- Licence:
- CC Attribution (CC BY)
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