TY - JOUR
T1 - Rp11-362k2.2:Rp11-767i20.1 genetic variation is associated with post-reperfusion therapy parenchymal hematoma. a gwas meta-analysis
AU - Muiño, Elena
AU - Cárcel-Márquez, Jara
AU - Carrera, C.
AU - Llucià-Carol, Laia
AU - Gallego-Fabrega, Cristina
AU - Cullell, Natalia
AU - Lledós, Miquel
AU - Castillo, J.
AU - Sobrino, T.
AU - Campos, Francisco
AU - Rodríguez-Castro, E.
AU - Millán, M.
AU - Muñoz-Narbona, L.
AU - Bustamante, Alejandro
AU - López-Cancio, E.
AU - Ribó, M.
AU - Álvarez Sabín, José
AU - Jiménez-Conde, J.
AU - Roquer, J.
AU - Giralt Steinhauer, Eva
AU - Soriano-Tárraga, C.
AU - Vives-Bauza, C.
AU - Díaz Navarro, R.
AU - Tur, S.
AU - Obach, V.
AU - Arenillas, Juan F..
AU - Segura, T.
AU - Serrano-Heras, G.
AU - Martí-Fàbregas, Joan
AU - Delgado Mederos, Raquel
AU - Camps-Renom, Pol
AU - Prats-Sánchez, Luis Antonio
AU - Guisado-Alonso, Daniel
AU - Guasch-Jiménez, Marina
AU - Marin, Rebeca
AU - Martínez-Domeño, Alejandro
AU - Freijo-Guerrero, M.D.M.
AU - Moniche, F.
AU - Cabezas, Juan Antonio
AU - Castellanos, M.
AU - Krupinsky, J.
AU - Strbian, D.
AU - Tatlisumak, T.
AU - Thijs, V.
AU - Lemmens, R.
AU - Slowik, A.
AU - Pera, J.
AU - Heitsch, Laura
AU - Ibañez, Laura
AU - Cruchaga, Carlos
AU - Dhar, R.
AU - Lee, J.M.
AU - Montaner, J.
AU - Fernandez-Cadenas, Israel
PY - 2021
Y1 - 2021
N2 - 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) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 × 10) 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.
AB - 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) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 × 10) 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.
KW - Hemorrhagic transformation
KW - Parenchymal hematoma
KW - GWAS
KW - Single nucleotide variants
U2 - 10.3390/jcm10143137
DO - 10.3390/jcm10143137
M3 - Article
C2 - 34300314
SN - 2077-0383
VL - 10
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 14
ER -