title: Stroke Genetics Network (SiGN) study: design and rationale for a genome-wide association study of ischemic stroke subtypes.
abstract: OBJECTIVE
  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.
authors.affiliation: From the Mayo Clinic Jacksonville, FL (J.F.M.); University of Alabama at Birmingham (D.K.A., L.A.M.); Mayo Clinic Rochester, MN (R.D.B.); Massachusetts General Hospital, Boston, MA (H.A., J.R., O.W.); University of British Columbia, Vancouver, British Columbia, Canada (O.R.B.); University of Maryland School of Medicine and Veterans Administration Medical Center, Baltimore, MD (J.W.C., P.F.M., B.D.M., A.R.S., S.J.K.); University Medical Center Utrecht, Utrecht, The Netherlands (P.I.W.d.B.); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (P.I.W.d.B.); Broad Institute of Harvard, MIT, Cambridge, MA (P.I.W.d.B.); Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D.); Johns Hopkins University, Baltimore, MD (K.F.D.); University of Texas Health Science Center at Houston (M.F.); Saint Francis Medical Center, Lynwood, CA (R.P.G.); NINDS Neurogenetics Cluster, Bethesda, MD (K.G.); IMIM-Hospital Universitari del Mar, Barcelona, Spain (J.J.C.); University of Florida, College of Pharmacy, Gainesville, FL (J.A.J.); Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Sweden (K.J., C.J.); University of Washington, Seattle, WA (C.C.L.); Washington University School of Medicine, St. Louis, MO (J.-M.L.); Lund University, Lund, Sweden (A.L.); St. George's University of London, London, United Kingdom (H.S.M.); Medical University Graz, Graz, Austria (R.S.); Brigham and Women's Hospital, Boston, MA (K.M.R.); University of Virginia, Charlottesville, VA (S.S.R., B.B.W.); Radcliffe Infirmary, Oxford, England (P.M.R.); University of Miami, Coral Gables, FL (T.R., R.L.S.); Imperial College London, London, United Kingdom (P.S.); Jagiellonian University, Krakow, Poland (A.S.); Albert Einstein College of Medicine, Bronx, NY (S.W.-S.); University of Edinburgh, Edinburgh, United Kingdom (C.S.); Universitaire Ziekenhuizen Leuven, Leuven, Belgium (V.N.S.T.); and University of Cincinnati, Cincinnati, OH (
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authors.lastname: Doheny
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authors.forename: Raji P
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authors.lastname: Grewal
authors.forename: Katrina
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authors.lastname: Gwinn
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authors.initials: C
authors.lastname: Jern
authors.forename: Jordi Jimenez
authors.initials: JJ
authors.lastname: Conde
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
authors.forename: Katarina
authors.initials: K
authors.lastname: Jood
authors.forename: Cathy C
authors.initials: CC
authors.lastname: Laurie
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Lee
authors.forename: Arne
authors.initials: A
authors.lastname: Lindgren
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
authors.forename: Patrick F
authors.initials: PF
authors.lastname: McArdle
authors.forename: Leslie A
authors.initials: LA
authors.lastname: McClure
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Rexrode
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.forename: Peter M
authors.initials: PM
authors.lastname: Rothwell
authors.forename: Tatjana
authors.initials: T
authors.lastname: Rundek
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sharma
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Slowik
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wassertheil-Smoller
authors.forename: Cathie
authors.initials: C
authors.lastname: Sudlow
authors.forename: Vincent N S
authors.initials: VN
authors.lastname: Thijs
authors.forename: Daniel
authors.initials: D
authors.lastname: Woo
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Worrall
authors.forename: Ona
authors.initials: O
authors.lastname: Wu
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authors.lastname: Kittner
mesh_terms: D002545:Brain Ischemia / Q000235:genetics*; D030561:Databases, Nucleic Acid; D055106:Genome-Wide Association Study / Q000379:methods / Q000592:standards; D005838:Genotype; D020407:Internet; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000235:genetics*
keywords: cerebral infarct; genetics; genomics
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