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REVIEW ARTICLE
Year : 2015  |  Volume : 1  |  Issue : 1  |  Page : 79-87

A molecular/genetic approach to cerebral small-vessel disease: Beyond aging and hypertension


1 Neurology Care Line; Center for Translational Research in Inflammatory Diseases (CTRID), Michael E. DeBakey Veterans Affairs Medical Center; Department of Neurology, Baylor College of Medicine, Houston, Texas, USA
2 Department of Neurology; Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA
3 Neurology Care Line, Michael E. DeBakey Veterans Affairs Medical Center; Department of Neurology; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
4 Department of Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, Ohio, USA

Correspondence Address:
Sharyl R Martini
Department of Veterans Affairs, Michael E. DeBakey VA Medical Center, Neurology Care Line, 2002 Holcombe Boulevard, MS 127 Houston, Texas - 77030-4211
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2394-8108.166376

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Lacunar infarction, white matter hyperintensities (WMH), deep cerebral microbleeds (dCMB), and deep intracerebral hemorrhage (ICH) are increasingly recognized as manifestations of a common underlying vasculopathy, encompassed by the term "cerebral small-vessel disease" (CSVD). Epidemiologic studies have found robust associations of the individual aspects of CSVD with aging and hypertension; however, heritability estimates and the disproportionate burden of CSVD in underrepresented minorities suggest that genetic factors contribute substantially to CSVD risk. Here we present the rationale for studying these phenotypes as part of a spectrum of CSVD, review aspects of genetic study design, summarize current knowledge of genetic contribution to CSVD, and discuss the next steps required to translate these genetic discoveries into therapies for this devastating disease. Genetic studies were identified using PubMed. Regions achieving genome-wide significance in association studies, meta-analyses of candidate gene studies, and studies of genes associated with Mendelian conditions exhibiting CSVD phenotypes have been summarized.


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