Show simple item record

dc.contributor.authorJohansson, Malin
dc.contributor.authorPedersen, Annie
dc.contributor.authorCole, John W
dc.contributor.authorLagging, Cecilia
dc.contributor.authorLindgren, Arne
dc.contributor.authorMaguire, Jane M
dc.contributor.authorRost, Natalia S
dc.contributor.authorSöderholm, Martin
dc.contributor.authorWorrall, Bradford B
dc.contributor.authorStanne, Tara M
dc.contributor.authorJern, Christina
dc.date.accessioned2021-11-19T19:46:42Z
dc.date.available2021-11-19T19:46:42Z
dc.date.issued2021-11-12
dc.identifier.urihttp://hdl.handle.net/10713/17185
dc.description.abstractBackground and objectives: To test the hypothesis that a predisposition to acquired genetic alterations is associated with ischemic stroke outcome by investigating the association between a polygenic risk score (PRS) for mosaic loss of chromosome Y (mLOY) and outcome in a large international data set. Methods: We used data from the genome-wide association study performed within the Genetics of Ischemic Stroke Functional Outcome network, which included 6,165 patients (3,497 men and 2,668 women) with acute ischemic stroke of mainly European ancestry. We assessed a weighted PRS for mLOY and examined possible associations with the modified Rankin Scale (mRS) score 3 months poststroke in logistic regression models. We investigated the whole study sample as well as men and women separately. Results: Increasing PRS for mLOY was associated with poor functional outcome (mRS score >2) with an odds ratio (OR) of 1.11 (95% confidence interval [CI] 1.03-1.19) per 1 SD increase in the PRS after adjustment for age, sex, ancestry, stroke severity (NIH Stroke Scale), smoking, and diabetes mellitus. In sex-stratified analyses, we found a statistically significant association in women (adjusted OR 1.20, 95% CI 1.08-1.33). In men, the association was in the same direction (adjusted OR 1.04, 95% CI 0.95-1.14), and we observed no significant genotype-sex interaction. Discussion: In this exploratory study, we found associations between genetic variants predisposing to mLOY and stroke outcome. The significant association in women suggests underlying mechanisms related to genomic instability that operate in both sexes. These findings need replication and mechanistic exploration.en_US
dc.description.urihttps://doi.org/10.1212/NXG.0000000000000634en_US
dc.description.urihttp://www.ncbi.nlm.nih.gov/pmc/articles/pmc8589264/en_US
dc.language.isoenen_US
dc.publisherWolters Kluwer Healthen_US
dc.relation.ispartofNeurology. Geneticsen_US
dc.rightsCopyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.en_US
dc.subject.meshClonal Hematopoiesisen_US
dc.subject.meshIschemic Stroke--geneticsen_US
dc.subject.meshSex Factorsen_US
dc.titleGenetic Predisposition to Mosaic Chromosomal Loss Is Associated With Functional Outcome After Ischemic Strokeen_US
dc.typeArticleen_US
dc.identifier.doi10.1212/NXG.0000000000000634
dc.identifier.pmid34786478
dc.source.volume7
dc.source.issue6
dc.source.beginpagee634
dc.source.endpage
dc.source.countryUnited States


This item appears in the following Collection(s)

Show simple item record