Shared and Distinct Genomics of Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Embolism.

Liley, James; Newnham, Michael; Bleda, Marta; Bunclark, Katherine; Auger, William; Barbera, Joan Albert; Bogaard, Harm; Delcroix, Marion; Fernandes, Timothy M; Howard, Luke; Jenkins, David; Lang, Irene; Mayer, Eckhard; Rhodes, Chris; Simpson, Michael; Southgate, Laura; Trembath, Richard; Wharton, John; Wilkins, Martin R; Gräf, Stefan; Morrell, Nicholas; Pepke Zaba, Joanna; Toshner, Mark

Abstract

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.

Citation

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