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Sökning: WFRF:(Rexrode Kathryn M) > Mitchell Braxton D.

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1.	Traylor, Matthew, et al. (författare) Genetic Variation at 16q24.2 is associated with small vessel stroke. 2017 Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 81:3 Tidskriftsartikel (refereegranskat)abstract Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises a quarter of all ischaemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown younger onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age-at-onset informed GWAS meta-analysis, including a large younger onset SVS population, to identify novel associations with stroke.We used a three-stage age-at-onset informed GWAS to identify novel genetic variants associated with stroke. On identifying a novel locus associated with SVS, we assessed its influence on other small vessel disease phenotypes, as well as on mRNA expression of nearby genes, and on DNA methylation of nearby CpG sites in whole blood and in the fetal brain.We identified an association with SVS in 4,203 cases and 50,728 controls on chromosome 16q24.2 (OR(95% CI)=1.16(1.10-1.22); p=3.2x10(-9) ). The lead SNP (rs12445022) was also associated with cerebral white matter hyperintensities (OR(95% CI)=1.10(1.05-1.16); p=5.3x10(-5) ; N=3,670), but not intracerebral haemorrhage (OR(95% CI)=0.97(0.84-1.12); p=0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p=9.4x10(-7) ), and DNA methylation at probe cg16596957 in whole blood (p=5.3x10(-6) ).16q24.2 is associated with SVS. Associations of the locus with expression of ZCCHC14 and DNA methylation suggest the locus acts through changes to regulatory elements. This article is protected by copyright. All rights reserved.
2.	Meschia, James F, et al. (författare) Stroke Genetics Network (SiGN) study: design and rationale for a genome-wide association study of ischemic stroke subtypes. 2013 Ingår i: Stroke; a journal of cerebral circulation. - 1524-4628. ; 44:10, s. 2694-702 Tidskriftsartikel (refereegranskat)abstract Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The National Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network) contributes substantially to meta-analyses that focus on specific subtypes of stroke.

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Typ av publikation: tidskriftsartikel (2)

Typ av innehåll: refereegranskat (2)

Författare/redaktör: Rothwell, Peter M. (2); Kittner, Steven J. (2); Meschia, James F (2); Jern, Christina, 196 ... (2); Dichgans, Martin (2); Rosand, Jonathan (2); visa fler...; Lindgren, Arne (2); Sharma, Pankaj (2); Cole, John W. (2); Worrall, Bradford B. (2); Slowik, Agnieszka (2); Schmidt, Reinhold (2); Woo, Daniel (2); Fornage, Myriam (2); Rich, Stephen S (2); de Bakker, Paul I. W ... (2); Johnson, Julie A. (2); Mitchell, Braxton D. (2); Grewal, Raji P. (2); Lee, Jin-Moo (2); Markus, Hugh S. (2); McArdle, Patrick F. (2); Rundek, Tatjana (2); Sacco, Ralph L. (2); Jood, Katarina, 1966 (1); Melander, Olle (1); Ikram, M. Arfan (1); Saleheen, Danish (1); Thorleifsson, Gudmar (1); Thorsteinsdottir, Un ... (1); Stefansson, Kari (1); Shuldiner, Alan R. (1); Spector, Tim D. (1); Laurie, Cathy C (1); Anderson, Christophe ... (1); Rost, Natalia S. (1); Radmanesh, Farid (1); Jimenez-Conde, Jordi (1); Launer, Lenore J (1); Pulit, Sara L. (1); Ay, Hakan (1); Sudlow, Cathie (1); Thijs, Vincent (1); Gwinn, Katrina (1); Lemmens, Robin (1); Levi, Chris (1); Rexrode, Kathryn M. (1); Longstreth, W.T. (1); Bell, Jordana T (1); Mill, Jonathan (1); visa färre...

Lärosäte: Göteborgs universitet (2); Lunds universitet (2)

Språk: Engelska (2)

Forskningsämne (UKÄ/SCB): Medicin och hälsovetenskap (2)

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