Genetic Study of White Matter Integrity in UK Biobank (N=8448) and the Overlap With Stroke, Depression, and Dementia

Stroke; a Journal of Cerebral Circulation
Loes C A Rutten-JacobsMatthew Traylor

Abstract

Structural integrity of the white matter is a marker of cerebral small vessel disease, which is the major cause of vascular dementia and a quarter of all strokes. Genetic studies provide a way to obtain novel insights in the disease mechanism underlying cerebral small vessel disease. The aim was to identify common variants associated with microstructural integrity of the white matter and to elucidate the relationships of white matter structural integrity with stroke, major depressive disorder, and Alzheimer disease. This genome-wide association analysis included 8448 individuals from UK Biobank-a population-based cohort study that recruited individuals from across the United Kingdom between 2006 and 2010, aged 40 to 69 years. Microstructural integrity was measured as fractional anisotropy- (FA) and mean diffusivity (MD)-derived parameters on diffusion tensor images. White matter hyperintensity volumes (WMHV) were assessed on T2-weighted fluid-attenuated inversion recovery images. We identified 1 novel locus at genome-wide significance (VCAN [versican]: rs13164785; P=3.7×10-18 for MD and rs67827860; P=1.3×10-14 for FA). LD score regression showed a significant genome-wide correlation between FA, MD, and WMHV (FA-WMHV rG 0.39 [SE...Continue Reading

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Citations

Jun 22, 2019·Stroke; a Journal of Cerebral Circulation·Robin B BrownHugh S Markus
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Datasets Mentioned

BETA
AG081220

Methods Mentioned

BETA
genotyping
chips

Software Mentioned

SNPTEST
IGAP
Almanac
Blood eQTL Browser Project eQTL Almanac
FSL
plink
IMPUTE4

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