Stroke Genetics Network (SiGN) Study
Authors: 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. ,   The SiGN study also includes the following collaborators, Anderson Christopher D. , Andren Kerstin , Andsberg Gunnar , Arsava Ethem , Barrett Kevin M. , Benner Thomas , Bentley Paul , Bevan Steven , Biffi Alessandro , Brenner David , Chapman Sherita , Cheng Yu-Ching , Delavaran Hossein , Deline Christopher , Dziedzic Tomasz , Gamble Dale , Giralt Eva , Grazer Anja , Gschwendtner Andreas , Hegge Caityln , Heitsch Laura , Helenius Johanna , Holmegaard Lukas , Huq Mohammed , Irie Robert E. , Jackson Rebecca , Katschnig Petra , Katsnelson Michael , Khoury Naim , Kilinc Selma , Kumar Gyanendra , Labovitz Daniel , Lanfranconi Silvia , Langefeld Carl D. , Lemmens Robin , Li Linxin , Malik Shaneela , Melander Olle , Nordstrom Sara , Norrving Bo , Ois Angel , Ossi Raid , Peddareddygari Leema Reddy , Pedersén Annie , Pera Joanna , Pucek Mateusz , Rannikmae Kristiina , Redfors Petra , Rhodes J. David , Ribasés Marta , Saraf Neha , Schuerks Markus , Seiler Stephan , Sheikh Huma , Southerland Andrew M , Sparks Mary J. , Stoegerer Eva , Sunyer Jordi , Temple Ella , Valenti Raffaella , Weir David , Weissman Darren , Woodfield Rebecca , Yiin Gabriel S.C 
Published: September 2013

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.