Dr James Liley james.liley@durham.ac.uk
Assistant Professor
Dr James Liley james.liley@durham.ac.uk
Assistant Professor
Michael Newnham
Marta Bleda
Katherine Bunclark
William Auger
Joan Albert Barbera
Harm Bogaard
Marion Delcroix
Timothy M Fernandes
Luke Howard
David Jenkins
Irene Lang
Eckhard Mayer
Chris Rhodes
Michael Simpson
Laura Southgate
Richard Trembath
John Wharton
Martin R Wilkins
Stefan Gräf
Nicholas Morrell
Joanna Pepke Zaba
Mark Toshner
Chronic Thromboembolic Pulmonary Hypertension involves formation and non-resolution of thrombus, dysregulated inflammation, angiogenesis and the development of a small vessel vasculopathy. We aimed to establish the genetic basis of chronic thromboembolic pulmonary hypertension to gain insight into its pathophysiological contributors. We conducted a genome-wide association study on 1907 European cases and 10363 European controls. We co-analysed our results with existing results from genome-wide association studies on deep vein thrombosis, pulmonary embolism and idiopathic pulmonary arterial hypertension. Our primary association study revealed genetic associations at the ABO, FGG, F11, MYH7B, and HLA-DRA loci. Through our co-analysis we demonstrate further associations with chronic thromboembolic pulmonary hypertension at the F2, TSPAN15, SLC44A2 and F5 loci but find no statistically significant associations shared with idiopathic pulmonary arterial hypertension. Chronic thromboembolic pulmonary hypertension is a partially heritable polygenic disease, with related though distinct genetic associations to pulmonary embolism and to deep vein thrombosis.
Liley, J., Newnham, M., Bleda, M., Bunclark, K., Auger, W., Barbera, J. A., Bogaard, H., Delcroix, M., Fernandes, T. M., Howard, L., Jenkins, D., Lang, I., Mayer, E., Rhodes, C., Simpson, M., Southgate, L., Trembath, R., Wharton, J., Wilkins, M. R., Gräf, S., …Toshner, M. (2024). Shared and Distinct Genomics of Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Embolism. American Journal of Respiratory and Critical Care Medicine, 209(12), 1477-1485. https://doi.org/10.1164/rccm.202307-1236OC
Journal Article Type | Article |
---|---|
Acceptance Date | Mar 11, 2024 |
Online Publication Date | Mar 17, 2024 |
Publication Date | Jun 15, 2024 |
Deposit Date | May 22, 2024 |
Publicly Available Date | May 22, 2024 |
Journal | American Journal of Respiratory and Critical Care Medicine |
Print ISSN | 1073-449X |
Electronic ISSN | 1535-4970 |
Publisher | American Thoracic Society |
Peer Reviewed | Peer Reviewed |
Volume | 209 |
Issue | 12 |
Pages | 1477-1485 |
DOI | https://doi.org/10.1164/rccm.202307-1236OC |
Keywords | Conditional false discovery rate, Pulmonary embolism, Chronic Thromboembolic Pulmonary Hypertension (CTEPH), Pulmonary Hypertension, Genome wide association study |
Public URL | https://durham-repository.worktribe.com/output/2367013 |
Accepted Journal Article
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This accepted manuscript is licensed under the Creative Commons Attribution 4.0 licence. https://creativecommons.org/licenses/by/4.0/
Published Journal Article
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http://creativecommons.org/licenses/by/4.0/
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