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

James Liley; 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

doi:10.1164/rccm.202307-1236OC

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

James Liley
, 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^*

^*Corresponding author for this work

Applied Health Sciences

Research output: Contribution to journal › Article › peer-review

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Abstract

Rationale: Chronic thromboembolic pulmonary hypertension involves the formation and nonresolution of thrombus, dysregulated inflammation, angiogenesis, and the development of a small-vessel vasculopathy.

Objectives: We aimed to establish the genetic basis of chronic thromboembolic pulmonary hypertension to gain insight into its pathophysiological contributors.

Methods: We conducted a genome-wide association study on 1,907 European cases and 10,363 European control subjects. We coanalyzed our results with existing results from genome-wide association studies on deep vein thrombosis, pulmonary embolism, and idiopathic pulmonary arterial hypertension.

Measurements and Main Results: Our primary association study revealed genetic associations at the ABO, FGG, F11, MYH7B, and HLA-DRA loci. Through our coanalysis, 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.

Conclusions: Chronic thromboembolic pulmonary hypertension is a partially heritable polygenic disease, with related though distinct genetic associations with pulmonary embolism and deep vein thrombosis.

Original language	English
Pages (from-to)	1477-1485
Number of pages	9
Journal	American Journal of Respiratory and Critical Care Medicine
Volume	209
Issue number	12
Early online date	12 Mar 2024
DOIs	https://doi.org/10.1164/rccm.202307-1236OC
Publication status	Published - 15 Jun 2024

Bibliographical note

Keywords

genome-wide association study
pulmonary arterial hypertension
venous thromboembolism

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine
Critical Care and Intensive Care Medicine

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LileyJ2024SharedFinal published version, 1.58 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

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., ... 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

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title = "Shared and Distinct Genomics of Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Embolism",

abstract = "Rationale: Chronic thromboembolic pulmonary hypertension involves the formation and nonresolution of thrombus, dysregulated inflammation, angiogenesis, and the development of a small-vessel vasculopathy.Objectives: We aimed to establish the genetic basis of chronic thromboembolic pulmonary hypertension to gain insight into its pathophysiological contributors.Methods: We conducted a genome-wide association study on 1,907 European cases and 10,363 European control subjects. We coanalyzed our results with existing results from genome-wide association studies on deep vein thrombosis, pulmonary embolism, and idiopathic pulmonary arterial hypertension.Measurements and Main Results: Our primary association study revealed genetic associations at the ABO, FGG, F11, MYH7B, and HLA-DRA loci. Through our coanalysis, 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.Conclusions: Chronic thromboembolic pulmonary hypertension is a partially heritable polygenic disease, with related though distinct genetic associations with pulmonary embolism and deep vein thrombosis.",

keywords = "genome-wide association study, pulmonary arterial hypertension, venous thromboembolism",

author = "James Liley and Michael Newnham and Marta Bleda and Katherine Bunclark and William Auger and Barbera, \{Joan Albert\} and Harm Bogaard and Marion Delcroix and Fernandes, \{Timothy M.\} and Luke Howard and David Jenkins and Irene Lang and Eckhard Mayer and Chris Rhodes and Michael Simpson and Laura Southgate and Richard Trembath and John Wharton and Wilkins, \{Martin R.\} and Stefan Gr{\"a}f and Nicholas Morrell and Zaba, \{Joanna Pepke\} and Mark Toshner",

note = "Publisher Copyright: Copyright {\textcopyright} 2024 by the American Thoracic Society.",

year = "2024",

month = jun,

day = "15",

doi = "10.1164/rccm.202307-1236OC",

language = "English",

volume = "209",

pages = "1477--1485",

journal = "American Journal of Respiratory and Critical Care Medicine",

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Liley, J, Newnham, M, Bleda, M, Bunclark, K, Auger, W, Barbera, JA, Bogaard, H, Delcroix, M, Fernandes, TM, Howard, L, Jenkins, D, Lang, I, Mayer, E, Rhodes, C, Simpson, M, Southgate, L, Trembath, R, Wharton, J, Wilkins, MR, Gräf, S, Morrell, N, Zaba, JP & Toshner, M 2024, 'Shared and Distinct Genomics of Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Embolism', American Journal of Respiratory and Critical Care Medicine, vol. 209, no. 12, pp. 1477-1485. https://doi.org/10.1164/rccm.202307-1236OC

TY - JOUR

T1 - Shared and Distinct Genomics of Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Embolism

AU - Liley, James

AU - Newnham, Michael

AU - Bleda, Marta

AU - Bunclark, Katherine

AU - Auger, William

AU - Barbera, Joan Albert

AU - Bogaard, Harm

AU - Delcroix, Marion

AU - Fernandes, Timothy M.

AU - Howard, Luke

AU - Jenkins, David

AU - Lang, Irene

AU - Mayer, Eckhard

AU - Rhodes, Chris

AU - Simpson, Michael

AU - Southgate, Laura

AU - Trembath, Richard

AU - Wharton, John

AU - Wilkins, Martin R.

AU - Gräf, Stefan

AU - Morrell, Nicholas

AU - Zaba, Joanna Pepke

AU - Toshner, Mark

PY - 2024/6/15

Y1 - 2024/6/15

N2 - Rationale: Chronic thromboembolic pulmonary hypertension involves the formation and nonresolution of thrombus, dysregulated inflammation, angiogenesis, and the development of a small-vessel vasculopathy.Objectives: We aimed to establish the genetic basis of chronic thromboembolic pulmonary hypertension to gain insight into its pathophysiological contributors.Methods: We conducted a genome-wide association study on 1,907 European cases and 10,363 European control subjects. We coanalyzed our results with existing results from genome-wide association studies on deep vein thrombosis, pulmonary embolism, and idiopathic pulmonary arterial hypertension.Measurements and Main Results: Our primary association study revealed genetic associations at the ABO, FGG, F11, MYH7B, and HLA-DRA loci. Through our coanalysis, 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.Conclusions: Chronic thromboembolic pulmonary hypertension is a partially heritable polygenic disease, with related though distinct genetic associations with pulmonary embolism and deep vein thrombosis.

AB - Rationale: Chronic thromboembolic pulmonary hypertension involves the formation and nonresolution of thrombus, dysregulated inflammation, angiogenesis, and the development of a small-vessel vasculopathy.Objectives: We aimed to establish the genetic basis of chronic thromboembolic pulmonary hypertension to gain insight into its pathophysiological contributors.Methods: We conducted a genome-wide association study on 1,907 European cases and 10,363 European control subjects. We coanalyzed our results with existing results from genome-wide association studies on deep vein thrombosis, pulmonary embolism, and idiopathic pulmonary arterial hypertension.Measurements and Main Results: Our primary association study revealed genetic associations at the ABO, FGG, F11, MYH7B, and HLA-DRA loci. Through our coanalysis, 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.Conclusions: Chronic thromboembolic pulmonary hypertension is a partially heritable polygenic disease, with related though distinct genetic associations with pulmonary embolism and deep vein thrombosis.

KW - genome-wide association study

KW - pulmonary arterial hypertension

KW - venous thromboembolism

UR - https://www.scopus.com/pages/publications/85196186299

U2 - 10.1164/rccm.202307-1236OC

DO - 10.1164/rccm.202307-1236OC

M3 - Article

C2 - 38470220

AN - SCOPUS:85196186299

SN - 1073-449X

VL - 209

SP - 1477

EP - 1485

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 12

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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Cite this