Journal of Clinical Medicine (Jul 2021)
<em>RP11-362K2.2:RP11-767I20.1</em> Genetic Variation Is Associated with Post-Reperfusion Therapy Parenchymal Hematoma. A GWAS Meta-Analysis
- Elena Muiño,
- Jara Cárcel-Márquez,
- Caty Carrera,
- Laia Llucià-Carol,
- Cristina Gallego-Fabrega,
- Natalia Cullell,
- Miquel Lledós,
- José Castillo,
- Tomás Sobrino,
- Francisco Campos,
- Emilio Rodríguez-Castro,
- Mònica Millán,
- Lucía Muñoz-Narbona,
- Alejandro Bustamante,
- Elena López-Cancio,
- Marc Ribó,
- José Álvarez-Sabín,
- Jordi Jiménez-Conde,
- Jaume Roquer,
- Eva Giralt-Steinhauer,
- Carolina Soriano-Tárraga,
- Cristófol Vives-Bauza,
- Rosa Díaz-Navarro,
- Silvia Tur,
- Victor Obach,
- Juan F. Arenillas,
- Tomás Segura,
- Gemma Serrano-Heras,
- Joan Martí-Fàbregas,
- Raquel Delgado-Mederos,
- Pol Camps-Renom,
- Luis Prats-Sánchez,
- Daniel Guisado,
- Marina Guasch,
- Rebeca Marin,
- Alejandro Martínez-Domeño,
- Maria del Mar Freijo-Guerrero,
- Francisco Moniche,
- Juan Antonio Cabezas,
- Mar Castellanos,
- Jerzy Krupinsky,
- Daniel Strbian,
- Turgut Tatlisumak,
- Vincent Thijs,
- Robin Lemmens,
- Agnieszka Slowik,
- Joanna Pera,
- Laura Heitsch,
- Laura Ibañez,
- Carlos Cruchaga,
- Rajat Dhar,
- Jin-Moo Lee,
- Joan Montaner,
- Israel Fernández-Cadenas,
- on behalf of International Stroke Genetic Consortium,
- the Spanish Stroke Genetic Consortium
Affiliations
- Elena Muiño
- Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
- Jara Cárcel-Márquez
- Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
- Caty Carrera
- Neurovascular Research Laboratory, VHIR, Universitat Autònoma de Barcelona, 08025 Barcelona, Spain
- Laia Llucià-Carol
- Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
- Cristina Gallego-Fabrega
- Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
- Natalia Cullell
- Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
- Miquel Lledós
- Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
- José Castillo
- Clinical Neurosciences Research Laboratories, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
- Tomás Sobrino
- Clinical Neurosciences Research Laboratories, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
- Francisco Campos
- Clinical Neurosciences Research Laboratories, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
- Emilio Rodríguez-Castro
- Department of Neurology, CHUS, 15706 Santiago de Compostela, Spain
- Mònica Millán
- Department of Neuroscience, HUGTP, 08025 Badalona, Spain
- Lucía Muñoz-Narbona
- Department of Neuroscience, HUGTP, 08025 Badalona, Spain
- Alejandro Bustamante
- Department of Neuroscience, HUGTP, 08025 Badalona, Spain
- Elena López-Cancio
- Stroke Unit, HUCA, 33011 Oviedo, Spain
- Marc Ribó
- Stroke Unit, HUVH, 08025 Barcelona, Spain
- José Álvarez-Sabín
- Department of Neurology, HUVH, UAB, 08025 Barcelona, Spain
- Jordi Jiménez-Conde
- Department of Neurology, Neurovascular Research Group, IMIM-Hospital del Mar, 08025 Barcelona, Spain
- Jaume Roquer
- Department of Neurology, Neurovascular Research Group, IMIM-Hospital del Mar, 08025 Barcelona, Spain
- Eva Giralt-Steinhauer
- Department of Neurology, Neurovascular Research Group, IMIM-Hospital del Mar, 08025 Barcelona, Spain
- Carolina Soriano-Tárraga
- Department of Neurology, Neurovascular Research Group, IMIM-Hospital del Mar, 08025 Barcelona, Spain
- Cristófol Vives-Bauza
- Neurobiology Laboratory, IdISPa, 07120 Mallorca, Spain
- Rosa Díaz-Navarro
- Department of Neurology, HUSE, 07120 Mallorca, Spain
- Silvia Tur
- Department of Neurology, HUSE, 07120 Mallorca, Spain
- Victor Obach
- Department of Neurology, Hospital Clínic i Provincial de Barcelona, 08025 Barcelona, Spain
- Juan F. Arenillas
- Department of Neurology, Hospital Clínico Universitario, University of Valladolid, 47003 Valladolid, Spain
- Tomás Segura
- Department of Neurology, CHUA, 02006 Albacete, Spain
- Gemma Serrano-Heras
- Experimental Research Unit, CHUA, 02006 Albacete, Spain
- Joan Martí-Fàbregas
- Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain
- Raquel Delgado-Mederos
- Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain
- Pol Camps-Renom
- Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain
- Luis Prats-Sánchez
- Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain
- Daniel Guisado
- Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain
- Marina Guasch
- Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain
- Rebeca Marin
- Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain
- Alejandro Martínez-Domeño
- Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain
- Maria del Mar Freijo-Guerrero
- Neurovascular Unit, Biocruces Bizkaia Health Research Institute, 48903 Bilbao, Spain
- Francisco Moniche
- Department of Neurology, Virgen del Rocío, IBIS, 41013 Seville, Spain
- Juan Antonio Cabezas
- Department of Neurology, Virgen del Rocío, IBIS, 41013 Seville, Spain
- Mar Castellanos
- Department of Neurology, CHUAC, 15006 A Coruña, Spain
- Jerzy Krupinsky
- School of Healthcare Science, Manchester Metropolitan University, Manchester M15 6BH, UK
- Daniel Strbian
- Department of Neurology, Helsinki University Hospital, FI-00029 Helsinki, Finland
- Turgut Tatlisumak
- Department of Clinical Neuroscience, Institute of Neurosciences and Physiology, Sahlgrenska Academy at University of Gothenburg, 41345 Gothenburg, Sweden
- Vincent Thijs
- Stroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, VIC 3072, Australia
- Robin Lemmens
- Department of Neurology, University Hospitals Leuven, Campus Gasthuisberg, 3000 Leuven, Belgium
- Agnieszka Slowik
- Department of Neurology, Jagiellonian University Medical College, 31-007 Kraków, Poland
- Joanna Pera
- Department of Neurology, Jagiellonian University Medical College, 31-007 Kraków, Poland
- Laura Heitsch
- Division of Emergency Medicine, Washington University School of Medicine, St. Louis, MO 63110-1010, USA
- Laura Ibañez
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110-1010, USA
- Carlos Cruchaga
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110-1010, USA
- Rajat Dhar
- Department of Neurology, Washington University School of Medicine, St. Louis MO 63110-1010, USA
- Jin-Moo Lee
- Department of Neurology, Washington University School of Medicine, St. Louis MO 63110-1010, USA
- Joan Montaner
- Department of Neurology, Virgen del Rocío, IBIS, 41013 Seville, Spain
- Israel Fernández-Cadenas
- Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
- on behalf of International Stroke Genetic Consortium
- the Spanish Stroke Genetic Consortium
- DOI
- https://doi.org/10.3390/jcm10143137
- Journal volume & issue
-
Vol. 10,
no. 14
p. 3137
Abstract
Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 × 10−8) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 × 10−8) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer’s disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-β, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases.
Keywords