on July 28, 2005
Published online before print July 28, 2005, doi: 10.1161/01.STR.0000177498.21594.9e
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Submitted on March 27, 2005
From the Department of Neurology (M.D.), Klinikum Gro * To whom correspondence should be addressed. E-mail: martin.dichgans{at}med.uni-muenchen.de.
Background and Purpose--A large number of candidate gene association studies have attempted to identify genes implicated in stroke, but there have been few replicable and robust associations reported. Summary of Review--The skantness of replicable associations partly relates to poor study design. Important methodological considerations include adequate sample size, the selection of appropriate controls, careful clinical phenotyping using standardized classification systems, and determining associations with stroke subtypes as well as stroke as a whole. The use of intermediate phenotypes, particularly carotid intima-media thickness and MRI white matter hyperintensities, appears promising. It is essential that positive associations are replicated in independent populations, and appropriate methodology is used in such studies. To be of use for others, association studies should meet certain standards. In particular, genetic association studies should enable replication studies and meta-analyses. Conclusions--This article discusses key methodological aspects and suggests standard criteria for candidate gene studies in stroke.
Revised on April 18, 2005
Accepted on April 21, 2005
Genetic Association Studies in Stroke. Methodological Issues and Proposed Standard Criteria
Martin Dichgans MD* and Hugh S. Markus FRCP
hadern, München, Germany; and Clinical Neuroscience (H.S.M.), St. George’s Hospital Medical School, London, UK.
Key words: genetics • stroke
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