RP11-362K2.2:RP11-767I20.1 genetic variation is associated with post-reperfusion therapy parenchymal hematoma. A GWAS meta-analysis

2021
journal article
article
10
dc.abstract.enStroke 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.
dc.affiliationWydział Lekarski : Zakład Neurogenetykipl
dc.cm.date2021-08-27
dc.cm.id105291
dc.cm.idOmegaUJCMcb90739a27df4a869439e244139fb5fcpl
dc.contributor.authorMuińo, Elenapl
dc.contributor.authorCárcel-Márquez, Jarapl
dc.contributor.authorCarrera, Catypl
dc.contributor.authorLluciŕ-Carol, Laiapl
dc.contributor.authorGallego-Fabrega, Cristinapl
dc.contributor.authorCullell, Nataliapl
dc.contributor.authorLledós, Miquelpl
dc.contributor.authorCastillo, Josépl
dc.contributor.authorSobrino, Tomáspl
dc.contributor.authorCampos, Franciscopl
dc.contributor.authorRodríguez-Castro, Emiliopl
dc.contributor.authorMillán, Mňnicapl
dc.contributor.authorMuńoz-Narbona, Lucíapl
dc.contributor.authorBustamante, Alejandropl
dc.contributor.authorLópez-Cancio, Elenapl
dc.contributor.authorRibó, Marcpl
dc.contributor.authorÁlvarez-Sabín, Josépl
dc.contributor.authorJiménez-Conde, Jordipl
dc.contributor.authorRoquer, Jaumepl
dc.contributor.authorGiralt-Steinhauer, Evapl
dc.contributor.authorSoriano-Tárraga, Carolinapl
dc.contributor.authorVives-Bauza, Cristófolpl
dc.contributor.authorDíaz Navarro, Rosapl
dc.contributor.authorTur, Silviapl
dc.contributor.authorObach, Victorpl
dc.contributor.authorArenillas, Juan F.pl
dc.contributor.authorSegura, Tomáspl
dc.contributor.authorSerrano-Heras, Gemmapl
dc.contributor.authorMartí-Fŕbregas, Joanpl
dc.contributor.authorDelgado-Mederos, Raquelpl
dc.contributor.authorCamps-Renom, Polpl
dc.contributor.authorPrats-Sánchez, Luispl
dc.contributor.authorGuisado, Danielpl
dc.contributor.authorGuasch, Marinapl
dc.contributor.authorMarin, Rebecapl
dc.contributor.authorMartínez-Domeńo, Alejandropl
dc.contributor.authordel Mar Freijo-Guerrero, Mariapl
dc.contributor.authorMoniche, Franciscopl
dc.contributor.authorCabezas, Juan Antoniopl
dc.contributor.authorCastellanos, Marpl
dc.contributor.authorKrupinsky, Jerzypl
dc.contributor.authorStrbian, Danielpl
dc.contributor.authorTatlisumak, Turgutpl
dc.contributor.authorThijs, Vincentpl
dc.contributor.authorLemmens, Robinpl
dc.contributor.authorSłowik, Agnieszka - 133430 pl
dc.contributor.authorPera, Joanna - 133117 pl
dc.contributor.authorHeitsch, Laurapl
dc.contributor.authorIbańez, Laurapl
dc.contributor.authorCruchaga, Carlospl
dc.contributor.authorDhar, Rajatpl
dc.contributor.authorLee, Jin-Moopl
dc.contributor.authorMontaner, Joanpl
dc.contributor.authorFernández-Cadenas, Israelpl
dc.date.accession2022-02-01pl
dc.date.accessioned2021-08-27T10:31:27Z
dc.date.available2021-08-27T10:31:27Z
dc.date.issued2021pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.number14pl
dc.description.points140
dc.description.versionostateczna wersja wydawcy
dc.description.volume10pl
dc.identifier.articleid3137pl
dc.identifier.doi10.3390/jcm10143137pl
dc.identifier.eissn2077-0383pl
dc.identifier.issn2077-0383pl
dc.identifier.projectROD UJ / Opl
dc.identifier.urihttps://ruj.uj.edu.pl/xmlui/handle/item/277769
dc.identifier.weblinkhttps://www.mdpi.com/2077-0383/10/14/3137/htmpl
dc.languageengpl
dc.language.containerengpl
dc.pbn.affiliationDziedzina nauk medycznych i nauk o zdrowiu : nauki medyczne
dc.relation.uri*
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.typeOtwarte czasopismo
dc.subject.enhemorrhagic transformation
dc.subject.enparenchymal hematoma
dc.subject.enGWAS
dc.subject.ensingle nucleotide variants
dc.subtypeArticlepl
dc.titleRP11-362K2.2:RP11-767I20.1 genetic variation is associated with post-reperfusion therapy parenchymal hematoma. A GWAS meta-analysispl
dc.title.journalJournal of Clinical Medicinepl
dc.typeJournalArticlepl
dspace.entity.typePublication
dc.abstract.en
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.
dc.affiliationpl
Wydział Lekarski : Zakład Neurogenetyki
dc.cm.date
2021-08-27
dc.cm.id
105291
dc.cm.idOmegapl
UJCMcb90739a27df4a869439e244139fb5fc
dc.contributor.authorpl
Muińo, Elena
dc.contributor.authorpl
Cárcel-Márquez, Jara
dc.contributor.authorpl
Carrera, Caty
dc.contributor.authorpl
Lluciŕ-Carol, Laia
dc.contributor.authorpl
Gallego-Fabrega, Cristina
dc.contributor.authorpl
Cullell, Natalia
dc.contributor.authorpl
Lledós, Miquel
dc.contributor.authorpl
Castillo, José
dc.contributor.authorpl
Sobrino, Tomás
dc.contributor.authorpl
Campos, Francisco
dc.contributor.authorpl
Rodríguez-Castro, Emilio
dc.contributor.authorpl
Millán, Mňnica
dc.contributor.authorpl
Muńoz-Narbona, Lucía
dc.contributor.authorpl
Bustamante, Alejandro
dc.contributor.authorpl
López-Cancio, Elena
dc.contributor.authorpl
Ribó, Marc
dc.contributor.authorpl
Álvarez-Sabín, José
dc.contributor.authorpl
Jiménez-Conde, Jordi
dc.contributor.authorpl
Roquer, Jaume
dc.contributor.authorpl
Giralt-Steinhauer, Eva
dc.contributor.authorpl
Soriano-Tárraga, Carolina
dc.contributor.authorpl
Vives-Bauza, Cristófol
dc.contributor.authorpl
Díaz Navarro, Rosa
dc.contributor.authorpl
Tur, Silvia
dc.contributor.authorpl
Obach, Victor
dc.contributor.authorpl
Arenillas, Juan F.
dc.contributor.authorpl
Segura, Tomás
dc.contributor.authorpl
Serrano-Heras, Gemma
dc.contributor.authorpl
Martí-Fŕbregas, Joan
dc.contributor.authorpl
Delgado-Mederos, Raquel
dc.contributor.authorpl
Camps-Renom, Pol
dc.contributor.authorpl
Prats-Sánchez, Luis
dc.contributor.authorpl
Guisado, Daniel
dc.contributor.authorpl
Guasch, Marina
dc.contributor.authorpl
Marin, Rebeca
dc.contributor.authorpl
Martínez-Domeńo, Alejandro
dc.contributor.authorpl
del Mar Freijo-Guerrero, Maria
dc.contributor.authorpl
Moniche, Francisco
dc.contributor.authorpl
Cabezas, Juan Antonio
dc.contributor.authorpl
Castellanos, Mar
dc.contributor.authorpl
Krupinsky, Jerzy
dc.contributor.authorpl
Strbian, Daniel
dc.contributor.authorpl
Tatlisumak, Turgut
dc.contributor.authorpl
Thijs, Vincent
dc.contributor.authorpl
Lemmens, Robin
dc.contributor.authorpl
Słowik, Agnieszka - 133430
dc.contributor.authorpl
Pera, Joanna - 133117
dc.contributor.authorpl
Heitsch, Laura
dc.contributor.authorpl
Ibańez, Laura
dc.contributor.authorpl
Cruchaga, Carlos
dc.contributor.authorpl
Dhar, Rajat
dc.contributor.authorpl
Lee, Jin-Moo
dc.contributor.authorpl
Montaner, Joan
dc.contributor.authorpl
Fernández-Cadenas, Israel
dc.date.accessionpl
2022-02-01
dc.date.accessioned
2021-08-27T10:31:27Z
dc.date.available
2021-08-27T10:31:27Z
dc.date.issuedpl
2021
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.numberpl
14
dc.description.points
140
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
10
dc.identifier.articleidpl
3137
dc.identifier.doipl
10.3390/jcm10143137
dc.identifier.eissnpl
2077-0383
dc.identifier.issnpl
2077-0383
dc.identifier.projectpl
ROD UJ / O
dc.identifier.uri
https://ruj.uj.edu.pl/xmlui/handle/item/277769
dc.identifier.weblinkpl
https://www.mdpi.com/2077-0383/10/14/3137/htm
dc.languagepl
eng
dc.language.containerpl
eng
dc.pbn.affiliation
Dziedzina nauk medycznych i nauk o zdrowiu : nauki medyczne
dc.relation.uri*
dc.rights
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
Otwarte czasopismo
dc.subject.en
hemorrhagic transformation
dc.subject.en
parenchymal hematoma
dc.subject.en
GWAS
dc.subject.en
single nucleotide variants
dc.subtypepl
Article
dc.titlepl
RP11-362K2.2:RP11-767I20.1 genetic variation is associated with post-reperfusion therapy parenchymal hematoma. A GWAS meta-analysis
dc.title.journalpl
Journal of Clinical Medicine
dc.typepl
JournalArticle
dspace.entity.type
Publication
Affiliations

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