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Genetic Predisposition to Mosaic Chromosomal Loss Is Associated with Functional Outcome after Ischemic Stroke

Johansson, Malin ; Pedersen, Annie ; Cole, John W. ; Lagging, Cecilia ; Lindgren, Arne LU ; Maguire, Jane M. ; Rost, Natalia S. ; Söderholm, Martin LU ; Worrall, Bradford B. and Stanne, Tara M. , et al. (2021) In Neurology: Genetics 7(6).
Abstract

Background and ObjectivesTo 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.MethodsWe 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... (More)

Background and ObjectivesTo 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.MethodsWe 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.ResultsIncreasing 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.DiscussionIn 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurology: Genetics
volume
7
issue
6
article number
e634
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:34786478
  • scopus:85121816669
ISSN
2376-7839
DOI
10.1212/NXG.0000000000000634
language
English
LU publication?
yes
additional info
Publisher Copyright: © American Academy of Neurology.
id
3ba29d0c-a923-44ff-b387-71c2c3cecb39
date added to LUP
2022-02-04 10:37:56
date last changed
2024-04-24 11:51:09
@article{3ba29d0c-a923-44ff-b387-71c2c3cecb39,
  abstract     = {{<p>Background and ObjectivesTo 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.MethodsWe 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.ResultsIncreasing PRS for mLOY was associated with poor functional outcome (mRS score &gt;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.DiscussionIn 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.</p>}},
  author       = {{Johansson, Malin and Pedersen, Annie and Cole, John W. and Lagging, Cecilia and Lindgren, Arne and Maguire, Jane M. and Rost, Natalia S. and Söderholm, Martin and Worrall, Bradford B. and Stanne, Tara M. and Jern, Christina}},
  issn         = {{2376-7839}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{6}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Neurology: Genetics}},
  title        = {{Genetic Predisposition to Mosaic Chromosomal Loss Is Associated with Functional Outcome after Ischemic Stroke}},
  url          = {{http://dx.doi.org/10.1212/NXG.0000000000000634}},
  doi          = {{10.1212/NXG.0000000000000634}},
  volume       = {{7}},
  year         = {{2021}},
}