Genomic Susceptibility Loci for Brain Atrophy, Ventricular Volume, and Leukoaraiosis in Hypertensive Sibships

Abstract

A multiplicity of vascular and neurodegenerative processes contributes to changes in brain structure with age. Despite success in identifying rare single gene mutations that cause stroke or dementia, most genes making smaller contributions to risk remain unknown.^1,2 Difficulties in identifying genetic polymorphisms with small effects on clinical end points are among the motivations for studying the underlying contributory disease processes, which progress asymptomatically for decades before a clinical event. Magnetic resonance imaging (MRI) of the brain has been used as a noninvasive method to obtain accurate and reproducible quantitative measures of alterations in brain structure, including cerebral atrophy, ventricular enlargement,³ and the volume of subcortical white matter hyperintensity (leukoaraiosis).⁴ These MRI measures of structural brain injury are heritable, associated with hypertension and other risk factors for arteriosclerosis, and predictive of stroke and dementia.^5,6