Stroke genetics network (SiGN) study design and rationale for a genome-wide association study of ischemic stroke subtypes

James F. Meschia, Donna K. Arnett, Hakan Ay, Robert D. Brown, Oscar R. Benavente, John W. Cole, Paul I W De Bakker, Martin Dichgans, Kimberly F. Doheny, Myriam Fornage, Raji P. Grewal, Katrina Gwinn, Christina Jern, Jordi Jimenez Conde, Julie A. Johnson, Katarina Jood, Cathy C. Laurie, Jin Moo Lee, Arne Lindgren, Hugh S. MarkusPatrick F. Mcardle, Leslie A. Mcclure, Braxton D. Mitchell, Reinhold Schmidt, Kathryn M. Rexrode, Stephen S. Rich, Jonathan Rosand, Peter M. Rothwell, Tatjana Rundek, Ralph L Sacco, Pankaj Sharma, Alan R. Shuldiner, Agnieszka Slowik, Sylvia Wassertheil-Smoller, Cathie Sudlow, Vincent N S Thijs, Daniel Woo, Bradford B. Worrall, Ona Wu, Steven J. Kittner

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2694-2702
Number of pages9
JournalStroke
Volume44
Issue number10
DOIs
StatePublished - Oct 1 2013

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Genome-Wide Association Study
Stroke
Genotype
National Institute of Neurological Disorders and Stroke
Genetic Research
Meta-Analysis
Genome
Phenotype
Information Centers
Genetic Association Studies
Biotechnology
Research
Information Systems
Single Nucleotide Polymorphism
Research Personnel
Databases

Keywords

  • Cerebral infarct
  • Genetics
  • Genomics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Meschia, J. F., Arnett, D. K., Ay, H., Brown, R. D., Benavente, O. R., Cole, J. W., ... Kittner, S. J. (2013). Stroke genetics network (SiGN) study design and rationale for a genome-wide association study of ischemic stroke subtypes. Stroke, 44(10), 2694-2702. https://doi.org/10.1161/STROKEAHA.113.001857

Stroke genetics network (SiGN) study design and rationale for a genome-wide association study of ischemic stroke subtypes. / Meschia, James F.; Arnett, Donna K.; Ay, Hakan; Brown, Robert D.; Benavente, Oscar R.; Cole, John W.; De Bakker, Paul I W; Dichgans, Martin; Doheny, Kimberly F.; Fornage, Myriam; Grewal, Raji P.; Gwinn, Katrina; Jern, Christina; Conde, Jordi Jimenez; Johnson, Julie A.; Jood, Katarina; Laurie, Cathy C.; Lee, Jin Moo; Lindgren, Arne; Markus, Hugh S.; Mcardle, Patrick F.; Mcclure, Leslie A.; Mitchell, Braxton D.; Schmidt, Reinhold; Rexrode, Kathryn M.; Rich, Stephen S.; Rosand, Jonathan; Rothwell, Peter M.; Rundek, Tatjana; Sacco, Ralph L; Sharma, Pankaj; Shuldiner, Alan R.; Slowik, Agnieszka; Wassertheil-Smoller, Sylvia; Sudlow, Cathie; Thijs, Vincent N S; Woo, Daniel; Worrall, Bradford B.; Wu, Ona; Kittner, Steven J.

In: Stroke, Vol. 44, No. 10, 01.10.2013, p. 2694-2702.

Research output: Contribution to journalArticle

Meschia, 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, JJ, Johnson, JA, Jood, K, Laurie, CC, Lee, JM, 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 2013, 'Stroke genetics network (SiGN) study design and rationale for a genome-wide association study of ischemic stroke subtypes', Stroke, vol. 44, no. 10, pp. 2694-2702. https://doi.org/10.1161/STROKEAHA.113.001857
Meschia, James F. ; Arnett, Donna K. ; Ay, Hakan ; Brown, Robert D. ; Benavente, Oscar R. ; Cole, John W. ; De Bakker, Paul I W ; Dichgans, Martin ; Doheny, Kimberly F. ; Fornage, Myriam ; Grewal, Raji P. ; Gwinn, Katrina ; Jern, Christina ; Conde, Jordi Jimenez ; Johnson, Julie A. ; Jood, Katarina ; Laurie, Cathy C. ; Lee, Jin Moo ; Lindgren, Arne ; Markus, Hugh S. ; Mcardle, Patrick F. ; Mcclure, Leslie A. ; Mitchell, Braxton D. ; Schmidt, Reinhold ; Rexrode, Kathryn M. ; Rich, Stephen S. ; Rosand, Jonathan ; Rothwell, Peter M. ; Rundek, Tatjana ; Sacco, Ralph L ; Sharma, Pankaj ; Shuldiner, Alan R. ; Slowik, Agnieszka ; Wassertheil-Smoller, Sylvia ; Sudlow, Cathie ; Thijs, Vincent N S ; Woo, Daniel ; Worrall, Bradford B. ; Wu, Ona ; Kittner, Steven J. / Stroke genetics network (SiGN) study design and rationale for a genome-wide association study of ischemic stroke subtypes. In: Stroke. 2013 ; Vol. 44, No. 10. pp. 2694-2702.
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AU - Meschia, James F.

AU - Arnett, Donna K.

AU - Ay, Hakan

AU - Brown, Robert D.

AU - Benavente, Oscar R.

AU - Cole, John W.

AU - De Bakker, Paul I W

AU - Dichgans, Martin

AU - Doheny, Kimberly F.

AU - Fornage, Myriam

AU - Grewal, Raji P.

AU - Gwinn, Katrina

AU - Jern, Christina

AU - Conde, Jordi Jimenez

AU - Johnson, Julie A.

AU - Jood, Katarina

AU - Laurie, Cathy C.

AU - Lee, Jin Moo

AU - Lindgren, Arne

AU - Markus, Hugh S.

AU - Mcardle, Patrick F.

AU - Mcclure, Leslie A.

AU - Mitchell, Braxton D.

AU - Schmidt, Reinhold

AU - Rexrode, Kathryn M.

AU - Rich, Stephen S.

AU - Rosand, Jonathan

AU - Rothwell, Peter M.

AU - Rundek, Tatjana

AU - Sacco, Ralph L

AU - Sharma, Pankaj

AU - Shuldiner, Alan R.

AU - Slowik, Agnieszka

AU - Wassertheil-Smoller, Sylvia

AU - Sudlow, Cathie

AU - Thijs, Vincent N S

AU - Woo, Daniel

AU - Worrall, Bradford B.

AU - Wu, Ona

AU - Kittner, Steven J.

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