Ischemic Stroke Genetics Study (ISGS)

The third leading cause of death in the United States, stroke is an acute neurological event leading to death of neural tissues.
Although the majority of strokes are ischemic strokes, meaning there is oxygen deprivation to the brain, almost 20% of strokes are
hemorrhagic, resulting from bleeding into the brain. Stroke is a complex disorder and likely multigenic in nature, resulting from
a combination of genetic and environmental factors. These well characterized risk factors that contribute to the incidence of stroke
include hypertension, cardiac disease, sickle cell disease, hyperhomocysteinemia, family history of stroke and smoking.

ISGS aim is to perform a prospective genetic association study of ischemic stroke focusing on the hemostatic system. ISGS
is a 5-center case-control study of first-ever ischemic stroke cases and concurrent controls individually matched for age,
sex and recruitment site.

This data includes that from subjects both banked in the
NINDS repository with biologicals publicly available, and those whose samples are not banked/not available.

This study utilized the NINDS Repository Cerebrovascular/Stroke Study,
and neurologically normal controls from the sample population which are banked in the National
Institute of Neurological Disorders and Stroke (NINDS Repository) collection for a first stage whole genome analysis.]]>
Participant Protection Policy FAQSAMPLE INFORMED CONSENT LANGUAGEControl Clinical Data ElementsSpetzler-Martin Grading ScoreCerebrovascular Disease ElementsA genome-wide high-density single-nucleotide-polymorphism (SNP) genotyping approach to a cohort of samples with and without ischemic stroke ( 278 cases from the Ischemic Stroke Genetics Study (ISGS) and 268 controls from the National Institute of Neurological Disorders and Stroke Neurogenetics Repository). An association analysis adjusting for known confounders was performed in a final cohort of 249 cases and 268 controls. More than 400,000 unique SNPs were assayed. All samples were assayed with the Illumina Infinium Human-1 and HumanHap300 SNP chips.ISGS Study Case eligibility criteria: Ischemic stroke was diagnosed according to World Health Organization definition
by history and physical examination, as well as by and findings on brain imaging (either head computed tomography or magnetic
resonance imaging). Subjects were eligible cases if they were over the age of 18 years and had a first-ever ischemic stroke with
onset of symptoms within 30 days of enrollment. The study excluded cases with postoperative or post-procedural stroke
(i.e., stroke related to cardiac catheterization, carotid stenting or conventional cerebral angiography); stroke related to recent
subarachnoid hemorrhage or mechanical heart valve (aortic or mitral); patients with known inherited stroke syndromes
(CADASIL, MELAS, Fabry disease, homocysteinemia, sickle cell anemia); and patients with biopsy-proven central nervous system
vasculitis or stroke occurring in the setting of active bacterial endocarditis.

ISGS Study Control Eligibility criteria: Controls were volunteers over the age of 18 years who have been verified
stroke-free by structured interview. This study excluded volunteers who were considered unreliable historians, who had a blood relative
enrolled as a case; and who were inpatients being treated for coronary or peripheral vascular disease. Controls needed to answer
negatively on all the items of the Questionnaire for Verifying Stroke-Free Status (Stroke 2000 May; 31(5): 1076-80).
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The ISGS protocol has been published in the peer-reviewed open access literature (BMC Neurology 2003), making the
primary aims a matter of public record and defining key phenotypic variables to foster collaborations with other investigators.
Our first study participant was enrolled on December 4, 2002. We achieved our recruitment goal of having 450 cases and 450 controls
individually matched for age, sex and site, almost 2 years ahead of schedule. After meeting this goal, we received approval
from our NINDS Project Officer to continue recruitment and re-budgeted accordingly. Over 1,300 participants were enrolled in the study.

The first genome-wide association study of ischemic stroke to be published (Lancet Neurol 2007; 6(5): 414-20) used
ISGS cases and this is the data made available here.

Funded by NINDS under grant # NINDS R01NS42733 and under contract N01-NS-2-2349, the "Human Genetics Resource Center: DNA and
Cell Line Repository".
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