Skip navigation
  •  Home
  • UDC 
    • Getting started
    • RUC Policies
    • FAQ
    • FAQ on Copyright
    • More information at INFOguias UDC
  • Browse 
    • Communities
    • Browse by:
    • Issue Date
    • Author
    • Title
    • Subject
  • Help
    • español
    • Gallegan
    • English
  • Login
  •  English 
    • Español
    • Galego
    • English
  
View Item 
  •   DSpace Home
  • Facultade de Ciencias da Saúde
  • Investigación (FCS)
  • View Item
  •   DSpace Home
  • Facultade de Ciencias da Saúde
  • Investigación (FCS)
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment

Thumbnail
View/Open
Gallego_Multitrait_2023.pdf (2.137Mb)
Gallego_Multitrait_2023_Suppl.zip - Supplementary material (1.815Mb)
Use this link to cite
http://hdl.handle.net/2183/37337
Creative Commons Attribution 4.0 International License (CC-BY 4.0)
Except where otherwise noted, this item's license is described as Creative Commons Attribution 4.0 International License (CC-BY 4.0)
Collections
  • Investigación (FCS) [1293]
Metadata
Show full item record
Title
A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment
Author(s)
Gallego-Fábrega, Cristina
Temprano-Sagrera, Gerard
Cárcel-Márquez, Jara
Muiño, Elena
Cullel, Natalia
Lledós, Miquel
Llucià-Carol, Laia
Martín-Campos, Jesús M.
Sobrino, Tomás
Castillo, José
Millán, Mónica
Muñoz-Narbona, Lucía
López-Cancio Martínez, Elena
Ribó, Marc
Álvarez-Sabín, José
Jiménez-Conde, Jordi
Roquer, Jaume
Tur, Silvia
Obach, Victor
Arenillas, Juan
Segura, Tomás
Serrano-Heras, Gemma
Martí-Fàbregas, Joan
Freijo Guerrero, María del Mar
Moniche Álvarez, Francisco
Castellanos, María del Mar
Morrison, Alana C.
Smith, Nicholas L.
de Vries, Paul S.
Fernández-Cadenas, Israel
Sabater-Lleal, María
Date
2023-12-15
Citation
Gallego-Fabrega C, Temprano-Sagrera G, Cárcel-Márquez J, Muiño E, Cullell N, Lledós M, Llucià-Carol L, Martin-Campos JM, Sobrino T, Castillo J, Millán M, Muñoz-Narbona L, López-Cancio E, Ribó M, Alvarez-Sabin J, Jiménez-Conde J, Roquer J, Tur S, Obach V, Arenillas JF, Segura T, Serrano-Heras G, Marti-Fabregas J, Freijo-Guerrero M, Moniche F, Castellanos MDM, Morrison AC, Smith NL, de Vries PS, Fernández-Cadenas I, Sabater-Lleal M; Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium; Spanish Stroke Genetic Consortium. A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment. J Thromb Haemost. 2024 Apr;22(4):936-950.
Abstract
[Abstract] Background: Thrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient's prognosis. Objectives: To investigate the association between genetically determined natural hemostatic factors' levels and increased risk of HT after r-tPA treatment. Methods: Using data from genome-wide association studies on the risk of HT after r-tPA treatment and data on 7 hemostatic factors (factor [F]VII, FVIII, von Willebrand factor [VWF], FXI, fibrinogen, plasminogen activator inhibitor-1, and tissue plasminogen activator), we performed local and global genetic correlation estimation multitrait analyses and colocalization and 2-sample Mendelian randomization analyses between hemostatic factors and HT. Results: Local correlations identified a genomic region on chromosome 16 with shared covariance: fibrinogen-HT, P = 2.45 × 10-11. Multitrait analysis between fibrinogen-HT revealed 3 loci that simultaneously regulate circulating levels of fibrinogen and risk of HT: rs56026866 (PLXND1), P = 8.80 × 10-10; rs1421067 (CHD9), P = 1.81 × 10-14; and rs34780449, near ROBO1 gene, P = 1.64 × 10-8. Multitrait analysis between VWF-HT showed a novel common association regulating VWF and risk of HT after r-tPA at rs10942300 (ZNF366), P = 1.81 × 10-14. Mendelian randomization analysis did not find significant causal associations, although a nominal association was observed for FXI-HT (inverse-variance weighted estimate [SE], 0.07 [-0.29 to 0.00]; odds ratio, 0.87; 95% CI, 0.75-1.00; raw P = .05). Conclusion: We identified 4 shared loci between hemostatic factors and HT after r-tPA treatment, suggesting common regulatory mechanisms between fibrinogen and VWF levels and HT. Further research to determine a possible mediating effect of fibrinogen on HT risk is needed.
Keywords
Fibrinogen
Hemorrhagic transformation
Hemostatic factors
r-tPA treatment
von Willebrand factor
 
Editor version
https://doi.org/10.1016/j.jtha.2023.11.027
Rights
Creative Commons Attribution 4.0 International License (CC-BY 4.0)
ISSN
1538-7933

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsResearch GroupAcademic DegreeThis CollectionBy Issue DateAuthorsTitlesSubjectsResearch GroupAcademic Degree

My Account

LoginRegister

Statistics

View Usage Statistics
Sherpa
OpenArchives
OAIster
Scholar Google
UNIVERSIDADE DA CORUÑA. Servizo de Biblioteca.    DSpace Software Copyright © 2002-2013 Duraspace - Send Feedback