NHLBI GO-ESP: Heart Cohorts Exome Sequencing Project (ISGS)

The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO. The Ischemic Stroke Genetics Study (ISGS) is a study of newly onset cases (~600) with ischemic stroke (a stroke due to sudden interruption of blood flow to a part of the brain) compared with sex- and age-matched non-stroke participants. The study was conducted to determine the genes and their variants that contribute to an individual's risk of developing an ischemic stroke. The coordination of the recruitment and flow of the samples occurred at the Mayo Clinic, Jacksonville, FL, under the direction of James F. Meschia, MD. The University of Virginia (Stephen S. Rich, PhD) served as the analytic site for the genetic data. All GWAS data on ISGS participants have been deposited into dbGaP. As part of the NHLBI Exome Sequencing Project, DNA from a subset of ISGS participants will undergo exome sequencing. For the NHLBI ESP, a subset of 92 individuals with lacunar (small vessel) or atherosclerotic (large vessel) TOAST subtypes were selected from among all ISGS participants, excluding those individuals with TOAST subtypes of stroke of other etiology or of stroke with undetermined etiology. All 92 samples pass initial quality control metrics and 89 samples completed exome sequencing. A total of 75 participants with appropriate consent and variant calls had their genetic and phenotypic data deposited into dbGaP.]]>
All cases had recent (within 30 days) first-ever ischemic stroke confirmed by history, physical examination, and head imaging (CT or MRI). Stroke was defined according to the World Health Organization (WHO) definition. Iatrogenic, septic embolic, vasospastic, and vasculitic stroke cases were excluded. The control cohort consisted of neurologically normal subjects derived from unrelated individuals from North America without a history of Alzheimer disease, amyotrophic lateral sclerosis, ataxia, autism, bipolar disorder, brain aneurysm, dementia, dystonia, Parkinson's disease, or stroke. None had any first-degree relative with a known primary neurological disorder.]]>
The Ischemic Stroke Genetics Study (ISGS) is a prospective five-center North American case-control study. The protocol for ISGS has been reported previously [Meschia JF, Brott TG, Brown RD, Jr, Crook RJ, Frankel M, Hardy J, Merino JG, Rich SS, Silliman S, Worrall BB. The Ischemic Stroke Genetics Study (ISGS) Protocol. BMC Neurol. 2003;3:4. PMID: 12848902].]]>