Imperial College London
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Dr Charlotte Dean

Faculty of Medicine, National Heart & Lung Institute

Reader in Lung Development and Disease
 
 
 
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Contact

 

+44 (0)20 7594 3174c.dean

 
 
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Location

 

110Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Portas:2020:10.1164/rccm.201912-2338OC,
author = {Portas, L and Pereira, M and Shaheen, SO and Wyss, AB and London, SJ and Burney, PGJ and Hind, M and Dean, CH and Minelli, C},
doi = {10.1164/rccm.201912-2338OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {853--865},
title = {Lung development genes and adult lung function},
url = {http://dx.doi.org/10.1164/rccm.201912-2338OC},
volume = {202},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - RATIONALE: Poor lung health in adult life may occur partly through suboptimal growth and development, as suggested by epidemiological evidence pointing to early life risk factors. OBJECTIVES: To systematically investigate the effects of lung development genes on adult lung function. METHODS: Using UK Biobank data, we tested the association of 391 genes known to influence lung development with FVC and FEV1/FVC. We split the 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. MEASUREMENTS AND MAIN RESULTS: We identified 55 genes, of which 36 (16 for FVC; 19 for FEV1/FVC; 1 for both) had not been identified in the largest, most recent genome-wide study of lung function. Most of these 36 signals were intronic variants; 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. CONCLUSIONS: Our study demonstrates the importance of lung development genes in regulating adult lung function and influencing both restrictive and obstructive patterns. Further investigation of these developmental pathways could lead to druggable targets.
AU  - Portas,L
AU  - Pereira,M
AU  - Shaheen,SO
AU  - Wyss,AB
AU  - London,SJ
AU  - Burney,PGJ
AU  - Hind,M
AU  - Dean,CH
AU  - Minelli,C
DO  - 10.1164/rccm.201912-2338OC
EP  - 865
PY  - 2020///
SN  - 1073-449X
SP  - 853
TI  - Lung development genes and adult lung function
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - http://dx.doi.org/10.1164/rccm.201912-2338OC
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32392078
UR  - https://www.atsjournals.org/doi/10.1164/rccm.201912-2338OC
UR  - http://hdl.handle.net/10044/1/79870
VL  - 202
ER  -
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