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Stroke DOI:10.1161/STROKEAHA.113.001857

Stroke Genetics Network (SiGN) study: design and rationale for a genome-wide association study of ischemic stroke subtypes.

Publication TypeJournal Article
Year of Publication2013
AuthorsMeschia, JF, Arnett, DK, Ay, H, Brown, RD, Benavente, OR, Cole, JW, de Bakker, PIW, Dichgans, M, Doheny, KF, Fornage, M, Grewal, RP, Gwinn, K, Jern, C, Conde, JJimenez, Johnson, JA, Jood, K, Laurie, CC, Lee, J-M, Lindgren, A, Markus, HS, McArdle, PF, McClure, LA, Mitchell, BD, Schmidt, R, Rexrode, KM, Rich, SS, Rosand, J, Rothwell, PM, Rundek, T, Sacco, RL, Sharma, P, Shuldiner, AR, Slowik, A, Wassertheil-Smoller, S, Sudlow, C, Thijs, VNS, Woo, D, Worrall, BB, Wu, O, Kittner, SJ
Corporate AuthorsNINDS SiGN Study
JournalStroke
Volume44
Issue10
Pages2694-702
Date Published2013 Oct
ISSN1524-4628
KeywordsBrain Ischemia, Databases, Nucleic Acid, Genome-Wide Association Study, Genotype, Internet, Polymorphism, Single Nucleotide, Stroke
Abstract

BACKGROUND AND PURPOSE: 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.

METHODS: The National Institute of Neurological Disorders and Stroke SiGN includes ischemic stroke cases from 24 genetic research centers: 13 from the United States and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the Web-based causative classification of stroke system, with data entered by trained and certified adjudicators at participating genetic research centers. Through the Center for Inherited Diseases Research, the Network plans to genotype 10,296 carefully phenotyped stroke cases using genome-wide single nucleotide polymorphism arrays and adds to these another 4253 previously genotyped cases, for a total of 14,549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. Center for Inherited Diseases Research-generated genotypes and corresponding phenotypes will be shared with the scientific community through the US National Center for Biotechnology Information database of Genotypes and Phenotypes, and brain MRI studies will be centrally archived.

CONCLUSIONS: The Stroke Genetics Network, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke.

URLhttp://stroke.ahajournals.org/cgi/pmidlookup?view=long&pmid=24021684
DOI10.1161/STROKEAHA.113.001857
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24021684?dopt=Abstract

Alternate JournalStroke
PubMed ID24021684
PubMed Central IDPMC4056331
Grant ListN01WH42124 / WH / WHI NIH HHS / United States
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U01 HG004446 / HG / NHGRI NIH HHS / United States
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