| Title: | New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries |
| Journal: | Nat Genet |
| Published: | 1 Mar 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30804560/ |
| DOI: | https://doi.org/10.1038/s41588-018-0321-7 |
Publication 1944
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Abstract
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 patient 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.Through new detailed quality control and analyses of spirometric measures of lung function in UK Biobank and expansion of the SpiroMeta Consortium, our study entailed a near seven-fold increase in sample size over previous studies of similar ancestry to address the following aims:
(i) to generate a high yield of genetic markers associated with lung function;
(ii) to confirm and fine-map previously reported lung function signals;
(iii) to investigate the putative causal genes and biological pathways through which lung function associated variants act, and their wider pleiotropic effects on other traits; and
(iv) to generate a weighted genetic risk score for lung function and test its association with COPD susceptibility in individuals of European and other ancestries.
1 Author
- Shrine N et al.
1 Application
| Application ID | Title |
|---|---|
| 648 | Common and rare genetic variants in respiratory health: the UK Biobank Lung Exome Variant Evaluation (UK BiLEVE) consortium |
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