A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype

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dc.contributor.author Cárcel-Márquez, J.
dc.contributor.author Muiño, E.
dc.contributor.author Gallego-Fabrega, C.
dc.contributor.author Cullell, N.
dc.contributor.author Lledós, M.
dc.contributor.author Llucià-Carol, L.
dc.contributor.author Sobrino, T.
dc.contributor.author Campos, F.
dc.contributor.author Castillo, J.
dc.contributor.author Freijo, M.
dc.contributor.author Arenillas, J.F.
dc.contributor.author Obach, V.
dc.contributor.author Álvarez-Sabín, J.
dc.contributor.author Molina, C.A.
dc.contributor.author Ribó, M.
dc.contributor.author Jiménez-Conde, J.
dc.contributor.author Roquer, J.
dc.contributor.author Muñoz-Narbona, L.
dc.contributor.author Lopez-Cancio, E.
dc.contributor.author Millán, M.
dc.contributor.author Diaz-Navarro, R.
dc.contributor.author Vives-Bauza, C.
dc.contributor.author Serrano-Heras, G.
dc.contributor.author Segura, T.
dc.contributor.author Ibañez, L.
dc.contributor.author Heitsch, L.
dc.contributor.author Delgado, P.
dc.contributor.author Dhar, R.
dc.contributor.author Krupinski, J.
dc.contributor.author Delgado-Mederos, R.
dc.contributor.author Prats-Sánchez, L.
dc.contributor.author Camps-Renom, P.
dc.contributor.author Blay, N.
dc.contributor.author Sumoy, L.
dc.contributor.author de Cid, R.
dc.contributor.author Montaner, J.
dc.contributor.author Cruchaga, C.
dc.contributor.author Lee, J.M.
dc.contributor.author Martí-Fàbregas, J.
dc.contributor.author Férnandez-Cadenas, I.
dc.date.accessioned 2022-08-03T05:57:35Z
dc.date.available 2022-08-03T05:57:35Z
dc.identifier.uri http://hdl.handle.net/11201/159526
dc.description.abstract [eng] Background: 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. Methods: 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 < 5 × 10-8 influencing both traits (GWAS-pairwise) with a p-value < 0.05 in the original GWAS and in an independent cohort (n = 9,105). The PRS was created with PRSice-2 and evaluated in the independent cohort. Results: 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. Conclusion: 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.
dc.format application/pdf
dc.relation.isformatof https://doi.org/10.3389/fcvm.2022.940696
dc.relation.ispartof Frontiers In Cardiovascular Medicine, 2022, vol. 9, num. 940696, p. 1-12
dc.rights , 2022
dc.subject.classification 61 - Medicina
dc.subject.other 61 - Medical sciences
dc.title A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype
dc.type info:eu-repo/semantics/article
dc.date.updated 2022-08-03T05:57:35Z
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.identifier.doi https://doi.org/10.3389/fcvm.2022.940696

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