The National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN)

The NINDS Stroke Genetics Network (SiGN) is a large international collaboration designed to detect genetic variants that predispose to subtypes of ischemic stroke. The study implements a genome wide association study (GWAS) methodology with all stroke cases undergoing phenotypic and stroke-subtype classification using the same web-based Causative Classification of Stroke (CCS) system, with data entered by trained and certified adjudicators at participating Research Centers (GRC's). SiGN includes ischemic stroke cases from 24 GRC's, 13 from the US and 11 from Europe. Each GRC has access to well-characterized ischemic stroke cases in which extensive phenotype data and high-quality DNA was available. Genome-wide data was available for many cases and for those without, new genome-wide genotyping, including exome chip genotyping of rare variants, was done through the Center for Inherited Diseases Research (CIDR). To maximize power for subtype analyses, genotyping resources were allocated almost exclusively to cases. With few exceptions, controls were drawn from studies with publicly available genome-wide data.

• Study Weblinks:
  • Stroke Genetics
• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
• dbGaP estimated ancestry using GRAF-pop
• Subject Sample Telemetry Report (SSTR)

Inclusion Criteria:

1. Ischemic stroke
2. Brain imaging with CT or MRI

Exclusion Criteria:

Cases due to rare known causes (including: dilated cardiomyopathy, infective endocarditis, papillary fibroelastoma, left atrial myxoma, cerebral vasculitis, cerebral venous thrombosis, acute disseminated intravascular coagulation, drug-induced, heparin-induced thrombocytopenia type II, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, iatrogenic causes, MELAS, meningitis, primary infection of the arterial wall, and sickle cell disease).

SiGN was established in response to a Request for Applications (RFA) issued by the NINDS that proposed establishing a genome-wide association study consortium focused on identifying genes or genomic regions that affect either the susceptibility to, or outcome of, ischemic stroke. The RFA specified that multiple Genetic Research Centers (GRC) be established that have access to well-characterized ischemic stroke cases in whom extensive phenotype, covariate, and exposure data are available and high-quality DNA is banked or could be isolated from stored specimen and that standardized, validated, and easily replicated methods should be used to assign stroke subtypes. The RFA further specified that investigators submit the harmonized phenotype data used for the stroke subtyping and the newly generated genotype data to the NIH-supported "database of Genotypes and Phenotypes" (dbGaP) to create a national resource of high quality information for data mining, replication studies, and future hypothesis generation.

• Primary Phenotype: Cerebral infarction

• BioProject
• BioSample
• MeSH

• Principal Investigator
  • Steven Kittner, MD. University of Maryland School of Medicine, Baltimore, MD, USA.
• Funding Source
  • 5UO1NS069208-02. National Institutes of Health, Bethesda, MD, USA.
• Genotyping Center
  • Center for Inherited Disease Research (CIDR). Johns Hopkins University, Baltimore, MD, USA.
• Funding Source for CIDR Genotyping
  • HHSN268201100011I. NIH contract "High throughput genotyping for studying the genetic contributions to human disease". National Institutes of Health, Bethesda, MD, USA.
• Genotyping Center Funding Source
  • HHSN268201200008I. National Institutes of Health, Bethesda, MD, USA.
• Genotyping Quality Control
  • Genetics Coordinating Center. Department of Biostatistics, University of Washington, WA, USA.