Genetics of Microangiopathic Brain Injury

Project: Research project

Project Details


This is a 2-year, revised-work scope competitive renewal for the Genetics of Microangiopathic Brain Injury
(GMBI) study, initially funded in 2001 as an ancillalY study to the Genetic Epidemiology Network of
Arteriopathy (GENOA) and Family Blood Pressure Program. In the initial GMBI grant cycle (2001-2006). we
conducted genomewide linkage analyses and candidate gene association analyses to identify genes
influencing leukoaraiosis, a heritable measure of ischemic brain injury determined by magnetic resonance
imaging (MRI) of subcortical white matter hyperintensity volume in 883 non-Hispanic white and 795 nonHispanic
black GMBI-GENOA participants ascertained through sibships with 2 or more members with essential
The 2[unreadable]year revised[unreadable]work scope research plan proposes a functional genomic strategy based on gene
expression measurements to identify genetic variants influencing leukoaraiosis and other MRI measures of
structural brain injury (cerebral atrophy and ventricular enlargement) associated with risk factors for
arteriosclerosis and predictive of stroke and dementia. The power of the proposed approach derives from
assessment of functional consequences of genomic variations associated with or linked to MRI measures of
structural brain injury.
Aim 1 will determine whether DNA sequence variants previously found to influence MRI measures of structural
brain injury may also have functional effects on heritable measures of gene expression in immortalized
lymphocytes from 883 white GMBI participants.
Aim 2 will determine whether inter[unreadable]individual variation in gene expression levels in immortalized lymphocytes,
which provide quantitative indices of the heritable, functional effects of multiple DNA sequence variations in a
gene region, are associated with MRI measures of structural brain injury in white GMBI participants.
Effective start/end date8/22/017/31/13


  • Medicine(all)
  • Neuroscience(all)