Study protocol
The Siblings With Ischemic Stroke Study (SWISS) Protocol
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* Corresponding author: James F Meschia meschia.james@mayo.edu
1 Department of Neurology, Mayo Clinic, Jacksonville, Florida
2 Department of Neurology, Mayo Clinic, Rochester, Minnesota
3 Luther Midelfort Clinic, Mayo Health System, Eau Claire, Wisconsin
4 National Institute on Aging, Bethesda, Maryland
5 Department of Public Health Sciences and Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
BMC Medical Genetics 2002, 3:1 doi:10.1186/1471-2350-3-1
Published: 12 February 2002Abstract
Background
Family history and twins studies suggest an inherited component to ischemic stroke risk. Candidate gene association studies have been performed but have limited capacity to identify novel risk factor genes. The Siblings With Ischemic Stroke Study (SWISS) aims to conduct a genome-wide scan in sibling pairs concordant or discordant for ischemic stroke to identify novel genetic risk factors through linkage analysis.
Methods
Screening at multiple clinical centers identifies patients (probands) with radiographically confirmed ischemic stroke and a family history of at least 1 living full sibling with stroke. After giving informed consent, without violating privacy among other family members, the proband invites siblings concordant and discordant for stroke to participate. Siblings then contact the study coordinating center. The diagnosis of ischemic stroke in potentially concordant siblings is confirmed by systematic centralized review of medical records. The stroke-free status of potentially discordant siblings is confirmed by validated structured telephone interview. Blood samples for DNA analysis are taken from concordant sibling pairs and, if applicable, from 1 discordant sibling. Epstein-Barr virus-transformed lymphoblastoid cell lines are created, and a scan of the human genome is planned.
Discussion
Conducting adequately powered genomics studies of stroke in humans is challenging because of the heterogeneity of the stroke phenotype and the difficulty of obtaining DNA samples from clinically well-characterized members of a cohort of stroke pedigrees. The multicentered design of this study is intended to efficiently assemble a cohort of ischemic stroke pedigrees without invoking community consent or using cold-calling of pedigree members.