Genetic Predisposition to Mosaic Chromosomal Loss Is Associated With Functional Outcome After Ischemic Stroke.

Johansson, M; Pedersen, A; Cole, JW; Lagging, C; Lindgren, A; Maguire, JM; Rost, NS; Söderholm, M; Worrall, BB; Stanne, TM; Jern, C

Genetic Predisposition to Mosaic Chromosomal Loss Is Associated With Functional Outcome After Ischemic Stroke.

Johansson, M Pedersen, A Cole, JW Lagging, C Lindgren, A Maguire, JM Rost, NS Söderholm, M Worrall, BB Stanne, TM Jern, C

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Publisher:: LIPPINCOTT WILLIAMS & WILKINS
Publication Type:: Journal Article
Citation:: Neurol Genet, 2021, 7, (6), pp. e634
Issue Date:: 2021-12

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Field	Value	Language
dc.contributor.author	Johansson, M
dc.contributor.author	Pedersen, A
dc.contributor.author	Cole, JW
dc.contributor.author	Lagging, C
dc.contributor.author	Lindgren, A
dc.contributor.author	Maguire, JM
dc.contributor.author	Rost, NS
dc.contributor.author	Söderholm, M
dc.contributor.author	Worrall, BB
dc.contributor.author	Stanne, TM
dc.contributor.author	Jern, C
dc.date.accessioned	2022-04-30T20:13:55Z
dc.date.available	2021-09-15
dc.date.available	2022-04-30T20:13:55Z
dc.date.issued	2021-12
dc.identifier.citation	Neurol Genet, 2021, 7, (6), pp. e634
dc.identifier.issn	2376-7839
dc.identifier.issn	2376-7839
dc.identifier.uri	http://hdl.handle.net/10453/156858
dc.description.abstract	Background 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.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	LIPPINCOTT WILLIAMS & WILKINS
dc.relation.ispartof	Neurol Genet
dc.relation.isbasedon	10.1212/NXG.0000000000000634
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0604 Genetics, 1109 Neurosciences
dc.title	Genetic Predisposition to Mosaic Chromosomal Loss Is Associated With Functional Outcome After Ischemic Stroke.
dc.type	Journal Article
utslib.citation.volume	7
utslib.location.activity	United States
utslib.for	0604 Genetics
utslib.for	1109 Neurosciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
utslib.copyright.status	open_access	*
dc.date.updated	2022-04-30T20:13:53Z
pubs.issue	6
pubs.publication-status	Published online
pubs.volume	7
utslib.citation.issue	6

Abstract:

Background 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.

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