Shared genetic susceptibility of vascular-related biomarkers with ischemic and recurrent stroke.

Williams, SR; Hsu, F-C; Keene, KL; Chen, W-M; Nelson, S; Southerland, AM; Madden, EB; Coull, B; Gogarten, SM; Furie, KL; Dzhivhuho, G; Rowles, JL; Mehndiratta, P; Malik, R; Dupuis, J; Lin, H; Seshadri, S; Rich, SS; Sale, MM; Worrall, BB; METASTROKE, The Genomics and Randomized Trials Network (GARNET) Collaborative Research Group,; METASTROKE The Genomics and Randomized Trials Network GARNET Collaborative Research Group,

Shared genetic susceptibility of vascular-related biomarkers with ischemic and recurrent stroke.

Williams, SR Hsu, F-C Keene, KL Chen, W-M Nelson, S Southerland, AM Madden, EB Coull, B Gogarten, SM Furie, KL Dzhivhuho, G Rowles, JL Mehndiratta, P Malik, R Dupuis, J Lin, H Seshadri, S Rich, SS Sale, MM Worrall, BB METASTROKE, The Genomics and Randomized Trials Network (GARNET) Collaborative Research Group, METASTROKE The Genomics and Randomized Trials Network GARNET Collaborative Research Group,

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Publisher:: LIPPINCOTT WILLIAMS & WILKINS
Publication Type:: Journal Article
Citation:: Neurology, 2016, 86, (4), pp. 351-359
Issue Date:: 2016-01-26

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Field	Value	Language
dc.contributor.author	Williams, SR
dc.contributor.author	Hsu, F-C
dc.contributor.author	Keene, KL
dc.contributor.author	Chen, W-M
dc.contributor.author	Nelson, S
dc.contributor.author	Southerland, AM
dc.contributor.author	Madden, EB
dc.contributor.author	Coull, B
dc.contributor.author	Gogarten, SM
dc.contributor.author	Furie, KL
dc.contributor.author	Dzhivhuho, G
dc.contributor.author	Rowles, JL
dc.contributor.author	Mehndiratta, P
dc.contributor.author	Malik, R
dc.contributor.author	Dupuis, J
dc.contributor.author	Lin, H
dc.contributor.author	Seshadri, S
dc.contributor.author	Rich, SS
dc.contributor.author	Sale, MM
dc.contributor.author	Worrall, BB
dc.contributor.author	METASTROKE, The Genomics and Randomized Trials Network (GARNET) Collaborative Research Group,
dc.contributor.author	METASTROKE The Genomics and Randomized Trials Network GARNET Collaborative Research Group,
dc.date.accessioned	2022-04-14T06:08:06Z
dc.date.available	2015-09-29
dc.date.available	2022-04-14T06:08:06Z
dc.date.issued	2016-01-26
dc.identifier.citation	Neurology, 2016, 86, (4), pp. 351-359
dc.identifier.issn	0028-3878
dc.identifier.issn	1526-632X
dc.identifier.uri	http://hdl.handle.net/10453/156261
dc.description.abstract	OBJECTIVE: To investigate the genetic contributors to cerebrovascular disease and variation in biomarkers of ischemic stroke. METHODS: The Vitamin Intervention for Stroke Prevention Trial (VISP) was a randomized, controlled clinical trial of B vitamin supplementation to prevent recurrent stroke, myocardial infarction, or death. VISP collected baseline measures of C-reactive protein (CRP), fibrinogen, creatinine, prothrombin fragments F1+2, thrombin-antithrombin complex, and thrombomodulin prior to treatment initiation. Genome-wide association scans were conducted for these traits and follow-up replication analyses were performed. RESULTS: We detected an association between CRP single nucleotide polymorphisms (SNPs) and circulating CRP levels (most associated SNP, rs2592902, p = 1.14 × 10(-9)) in 2,100 VISP participants. We discovered a novel association for CRP level in the AKR1D1 locus (rs2589998, p = 7.3 × 10(-8), approaching genome-wide significance) that also is an expression quantitative trait locus for CRP gene expression. We replicated previously identified associations of fibrinogen with SNPs in the FGB and LEPR loci. CRP-associated SNPs and CRP levels were significantly associated with risk of ischemic stroke and recurrent stroke in VISP as well as specific stroke subtypes in METASTROKE. Fibrinogen levels but not fibrinogen-associated SNPs were also found to be associated with recurrent stroke in VISP. CONCLUSIONS: Our data identify a genetic contribution to inflammatory and hemostatic biomarkers in a stroke population. Additionally, our results suggest shared genetic contributions to circulating CRP levels measured poststroke and risk for incident and recurrent ischemic stroke. These data broaden our understanding of genetic contributors to biomarker variation and ischemic stroke risk, which should be useful in clinical risk evaluation.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	LIPPINCOTT WILLIAMS & WILKINS
dc.relation.ispartof	Neurology
dc.relation.isbasedon	10.1212/WNL.0000000000002319
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1103 Clinical Sciences, 1109 Neurosciences, 1702 Cognitive Sciences
dc.subject.classification	Neurology & Neurosurgery
dc.subject.mesh	Aged
dc.subject.mesh	Biomarkers
dc.subject.mesh	Brain Ischemia
dc.subject.mesh	C-Reactive Protein
dc.subject.mesh	Female
dc.subject.mesh	Fibrinogen
dc.subject.mesh	Gene Expression
dc.subject.mesh	Genetic Loci
dc.subject.mesh	Genetic Predisposition to Disease
dc.subject.mesh	Genome-Wide Association Study
dc.subject.mesh	Humans
dc.subject.mesh	Male
dc.subject.mesh	Middle Aged
dc.subject.mesh	Oxidoreductases
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Randomized Controlled Trials as Topic
dc.subject.mesh	Recurrence
dc.subject.mesh	Stroke
dc.subject.mesh	Humans
dc.subject.mesh	Brain Ischemia
dc.subject.mesh	Genetic Predisposition to Disease
dc.subject.mesh	Recurrence
dc.subject.mesh	Oxidoreductases
dc.subject.mesh	C-Reactive Protein
dc.subject.mesh	Fibrinogen
dc.subject.mesh	Gene Expression
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Aged
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Randomized Controlled Trials as Topic
dc.subject.mesh	Stroke
dc.subject.mesh	Genome-Wide Association Study
dc.subject.mesh	Genetic Loci
dc.subject.mesh	Biomarkers
dc.title	Shared genetic susceptibility of vascular-related biomarkers with ischemic and recurrent stroke.
dc.type	Journal Article
utslib.citation.volume	86
utslib.location.activity	United States
utslib.for	1103 Clinical Sciences
utslib.for	1109 Neurosciences
utslib.for	1702 Cognitive Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
utslib.copyright.status	closed_access	*
dc.date.updated	2022-04-14T06:08:04Z
pubs.issue	4
pubs.publication-status	Published
pubs.volume	86
utslib.citation.issue	4

Abstract:

OBJECTIVE: To investigate the genetic contributors to cerebrovascular disease and variation in biomarkers of ischemic stroke. METHODS: The Vitamin Intervention for Stroke Prevention Trial (VISP) was a randomized, controlled clinical trial of B vitamin supplementation to prevent recurrent stroke, myocardial infarction, or death. VISP collected baseline measures of C-reactive protein (CRP), fibrinogen, creatinine, prothrombin fragments F1+2, thrombin-antithrombin complex, and thrombomodulin prior to treatment initiation. Genome-wide association scans were conducted for these traits and follow-up replication analyses were performed. RESULTS: We detected an association between CRP single nucleotide polymorphisms (SNPs) and circulating CRP levels (most associated SNP, rs2592902, p = 1.14 × 10(-9)) in 2,100 VISP participants. We discovered a novel association for CRP level in the AKR1D1 locus (rs2589998, p = 7.3 × 10(-8), approaching genome-wide significance) that also is an expression quantitative trait locus for CRP gene expression. We replicated previously identified associations of fibrinogen with SNPs in the FGB and LEPR loci. CRP-associated SNPs and CRP levels were significantly associated with risk of ischemic stroke and recurrent stroke in VISP as well as specific stroke subtypes in METASTROKE. Fibrinogen levels but not fibrinogen-associated SNPs were also found to be associated with recurrent stroke in VISP. CONCLUSIONS: Our data identify a genetic contribution to inflammatory and hemostatic biomarkers in a stroke population. Additionally, our results suggest shared genetic contributions to circulating CRP levels measured poststroke and risk for incident and recurrent ischemic stroke. These data broaden our understanding of genetic contributors to biomarker variation and ischemic stroke risk, which should be useful in clinical risk evaluation.

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http://hdl.handle.net/10453/156261