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  • Title: Analysis of genetic variability and whole genome linkage of whole-brain, subcortical, and ependymal hyperintense white matter volume.
    Author: Kochunov P, Glahn D, Winkler A, Duggirala R, Olvera RL, Cole S, Dyer TD, Almasy L, Fox PT, Blangero J.
    Journal: Stroke; 2009 Dec; 40(12):3685-90. PubMed ID: 19834011.
    Abstract:
    BACKGROUND AND PURPOSE: The cerebral volume of T2-hyperintense white matter (HWM) is an important neuroimaging marker of cerebral integrity. Pathophysiology studies identified that subcortical and ependymal HWM are produced by 2 different mechanisms but shared a common risk factor: high arterial pulse pressure. Recent studies have demonstrated high heritability of the whole-brain HMW volume and reported significant and suggestive evidence of genetic linkage. We performed heritability and whole-genome linkage analysis to replicate previous reported findings and to study shared genetic variance, and possible overlap for specific loci, between subcortical and ependymal HWM volumes in a population of healthy Mexican Americans. METHODS: The volumes of subcortical and ependymal HWM regions were measured from high-resolution (1 mm(3)), 3-dimensional fluid-attenuated inversion recovery images acquired for 459 (283 females, 176 males) active participants in the San Antonio Family Heart Study. Subjects ranged in age from 19 to 85 years of age (47.9+/-13.5 years) and were part of 49 families (9.4+/-8.5 individuals per family). RESULTS: The volumes of whole-brain, subcortical, and ependymal HWM were highly heritable (h(2)=0.72, 0.66, and 0.73, respectively). The subcortical and ependymal HWM volumes shared 21% of genetic variability indicating significant pleiotropy. Genomewide linkage analysis showed only a suggestive bivariate linkage for subcortical and ependymal HWM volumes (log of odds=2.12) on chromosome 1 at 288 cM. CONCLUSIONS: We replicated previous findings of high heritability for the whole-brain HWM volume. We also showed that subcortical and ependymal volume shared a significant portion of genetic variability and the bivarate linkage analysis produced a suggestive linkage near the locus previously identified in a study of whole-brain HWM volume and arterial pulse pressure.
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