Contribution of common genetic variants to risk of early onset ischemic stroke

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• dc.contributor.author Jaworek, Thomas
• dc.contributor.author Jiménez Conde, Jordi
• dc.contributor.author Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC)
• dc.date.accessioned 2023-02-10T07:30:40Z
• dc.date.available 2023-02-10T07:30:40Z
• dc.date.issued 2022
• dc.description.abstract Background and objectives: Current genome-wide association studies of ischemic stroke have focused primarily on late onset disease. As a complement to these studies, we sought to identifythe contribution of common genetic variants to risk of early onset ischemic stroke. Methods: We performed a meta-analysis of genome-wide association studies of early onset stroke (EOS), ages 18-59, using individual level data or summary statistics in 16,730 cases and 599,237 non-stroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late onset stroke (LOS) and compared polygenic risk scores for venous thromboembolism between EOS and LOS. Results: We observed genome-wide significant associations of EOS with two variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared to LOS. The odds ratio (OR) for rs529565, tagging O1, 0.88 (95% CI: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared to LOS (p=0.008). Discussion: The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
• dc.format.mimetype application/pdf
• dc.identifier.citation Jaworek T, Xu H, Gaynor BJ, Cole JW, Rannikmae K, Stanne TM, et al. Contribution of common genetic variants to risk of early onset ischemic stroke. Neurology. 2022 Aug 31;99(16):e1738-54. DOI: 10.1212/WNL.0000000000201006
• dc.identifier.doi http://dx.doi.org/10.1212/WNL.0000000000201006
• dc.identifier.issn 0028-3878
• dc.identifier.uri http://hdl.handle.net/10230/55710
• dc.language.iso eng
• dc.publisher Wolters Kluwer (LWW)
• dc.relation.ispartof Neurology. 2022 Aug 31;99(16):e1738-54
• dc.rights © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Infarction
• dc.subject.keyword Association studies in genetics
• dc.subject.keyword Stroke in young adults
• dc.title Contribution of common genetic variants to risk of early onset ischemic stroke
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion