| Title: | Lung Development Genes and Adult Lung Function |
| Journal: | Am J Respir Crit Care Med |
| Published: | 15 Sep 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32392078/ |
| DOI: | https://doi.org/10.1164/rccm.201912-2338OC |
Publication 3611
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Abstract
Epidemiological evidence suggests that poor lung function and lung disease in adult life may occur partly through suboptimal growth and development. We systematically investigated the effects of lung development genes on adult lung function.Using data from UK Biobank, we tested the association of 391 genes known to influence lung development based on animal and human evidence, with FVC and FEV1/FVC. We split the available dataset into two random subsets of 207,616 and 138,411 individuals, using the larger to select the most promising signals and the smaller for replication.
Overall, we identified 55 lung development related genes associated with adult lung function; of which 36 are novel (16 for FVC; 19 for FEV1/FVC; 1 for both), showing the value of our hypothesis-driven approach in complementing agnostic GWAS. Most of these 36 signals were intronic variants and expression data from blood and lung tissue showed that the majority affect the expression of the genes they lie within. Further testing of 34 of these 36 signals in the CHARGE and SpiroMeta consortia showed that 16 replicated after Bonferroni correction and another 12 at nominal significance level. 53 of the 55 genes fell into four biological categories whose function is to regulate organ size and cell integrity (growth factors; transcriptional regulators; cell-cell adhesion; extra-cellular matrix), suggesting that these specific processes are important for adult lung health.
Our study demonstrates the role of lung development genes in regulating adult lung function and influencing both restrictive and obstructive patterns; their further investigation might lead to druggable targets.
1 Author
- Portas L et al.
1 Application
| Application ID | Title |
|---|---|
| 19136 | Lung Health: Genes and environment |
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