RT Journal Article
T1 A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype.
A1 Carcel-Marquez, Jara
A1 Muiño, Elena
A1 Gallego-Fabrega, Cristina
A1 Cullell, Natalia
A1 Lledos, Miquel
A1 Llucia-Carol, Laia
A1 Sobrino, Tomas
A1 Campos, Francisco
A1 Castillo, Jose
A1 Freijo, Marimar
A1 Arenillas, Juan Francisco
A1 Obach, Victor
A1 Alvarez-Sabin, Jose
A1 Molina, Carlos A
A1 Ribo, Marc
A1 Jimenez-Conde, Jordi
A1 Roquer, Jaume
A1 Muñoz-Narbona, Lucia
A1 Lopez-Cancio, Elena
A1 Millan, Monica
A1 Diaz-Navarro, Rosa
A1 Vives-Bauza, Cristofol
A1 Serrano-Heras, Gemma
A1 Segura, Tomas
A1 Ibañez, Laura
A1 Heitsch, Laura
A1 Delgado, Pilar
A1 Dhar, Rajat
A1 Krupinski, Jerzy
A1 Delgado-Mederos, Raquel
A1 Prats-Sanchez, Luis
A1 Camps-Renom, Pol
A1 Blay, Natalia
A1 Sumoy, Lauro
A1 de Cid, Rafael
A1 Montaner, Joan
A1 Cruchaga, Carlos
A1 Jin-Moo, Lee
A1 Marti-Fabregas, Joan
A1 Fernandez-Cadenas, Israel
K1 ESUs
K1 GWAS
K1 multi-trait analysis
K1 polygenic risk score
K1 stroke
AB Occult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification. Multitrait analysis of GWAS (MTAG) was performed with MEGASTROKE-CES cohort (n = 362,661) and AF cohort (n = 1,030,836). We considered significant variants and replicated those variants with MTAG p-value  We found and replicated eleven loci associated with CES. Eight were novel loci. Seven of them had been previously associated with AF, namely, CAV1, ESR2, GORAB, IGF1R, NEURL1, WIPF1, and ZEB2. KIAA1755 locus had never been associated with CES/AF, leading its index variant to a missense change (R1045W). The PRS generated has been significantly associated with CES improving discrimination and patient reclassification of a model with age, sex, and hypertension. The loci found significantly associated with CES in the MTAG, together with the creation of a PRS that improves the predictive clinical models of CES, might help guide future clinical trials of anticoagulant therapy in patients with ESUS or AF.
PB Frontiers Research Foundation
SN 2297-055X
YR 2022
FD 2022-07-08
LK http://hdl.handle.net/10668/20554
UL http://hdl.handle.net/10668/20554
LA en
NO Cárcel-Márquez J, Muiño E, Gallego-Fabrega C, Cullell N, Lledós M, Llucià-Carol L, et al. A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype. Front Cardiovasc Med. 2022 Jul 8;9:940696.
DS RISalud
RD Apr 10, 2025