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ARTICLES: Ahamad Hassan, Pak C. Sham, and Hugh S. Markus Planning genetic studies in human stroke: Sample size estimates based on family history data Neurology 2002; 58: 1483-1488 [Abstract] [Full text] [PDF]

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Planning genetic studies in human stroke: Sample size estimates based on family history data

James F Meschia, Thomas G Brott, Robert D Brown Jr, Brett M Kissela, Stephen S Rich   (24 June 2002)

Planning genetic studies in human stroke: Sample size estimates based on family history data 24 June 2002
James F Meschia Mayo Clinic Jacksonville FL, Thomas G Brott, Robert D Brown Jr, Brett M Kissela, Stephen S Rich Send Correspondence to journal: Re: Planning genetic studies in human stroke: Sample size estimates based on family history data Meschia.James{at}mayo.edu James F Meschia, et al.	Rigorous determination of the molecular basis for inherited stroke risk will be challenging. Within this context, Hassan et al. are to be commended for their recent contribution to a burgeoning literature. [1] Our research supports their conclusion that the affected sib-pair methodology may require large multi-center collaborations. [2] We previously collected family history data in 310 consecutive patients with ischemic stroke at two centers, and these preliminary data guided the design and implementation of a large multi-center affected sib-pair study of ischemic stroke. Supported by the National Institute of Neurological Disorders and Stroke, the Siblings with Ischemic Stroke Study (SWISS) are actively recruiting probands and siblings with recent ischemic stroke. [3, 4] A total of 51 clinical centers from 24 states across the US and three provinces in Canada are currently enrolling patients. We have found that the multi-centered approach to pedigree ascertainment can lead to the recruitment of a diverse population. Analysis of the first 197 probands enrolled demonstrated that the proband median age was 67 +/- 11 years (mean 67.7 years). Forty-five percent of the probands were women, and 21% of the probands were non-Caucasian. Proband stroke subtypes were: large artery atherosclerosis, 30%; cardioembolism, 9%; small artery occlusion, 36%; other determined etiology, 4%; and undetermined etiology, 21% (TOAST criteria). [5] By May 2002, 253 probands had been enrolled in the SWISS, and 140 cell lines had been created. DNA samples have been collected from 55 sibling pairs concordant for CT- or MR-confirmed ischemic stroke. Ongoing support of studies such as SWISS will allow clarification of the genetic contribution to a common, potentially devastating disorder. References: 1)Hassan A, Sham PC, Markus HS. Planning genetic studies in human stroke: Sample size estimates based on family history data. Neurology 2002;58:1483-1488. 2)Meschia JF, Brown RD Jr, Brott TG, Hardy J, Atkinson EJ, O’Brien PC. Feasibility of an affected sibling pair study in ischemic stroke: Results of a 2-center family history registry. Stroke 2001;32:2939-2941. 3)Major Ongoing Stroke Trials. Stroke 2002;33:652-653. 4)Meschia JF, Brown RD Jr, Brott TG, Chukwudelunzu FE, Hardy J, Rich SS. The Siblings with Ischemic Stroke Study (SWISS) Protocol. BMC Med Genet 2002;3:1. 5)Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke: Definitions for use in a multicenter clinical trial. Stroke 1993;24:35-41.