Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure

Warstadt, N. M., Dennis, E. L., Jahanshad, N., Kohannim, O., Nir, T. M., McMahon, K. L., de Zubicaray, G. I., Montgomery, G. W., Henders, A. K., Martin, N. G., Whitfield, J. B., Jack, C. R., Bernstein, M. A., Weiner, M. W., Toga, A. W., Wright, M. J., & Thompson, P. M. (2014) Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure. Neurobiology of Aging, 35(11), pp. 2504-2513.

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Abstract

Several common genetic variants influence cholesterol levels, which play a key role in overall health. Myelin synthesis and maintenance are highly sensitive to cholesterol concentrations, and abnormal cholesterol levels increase the risk for various brain diseases, including Alzheimer's disease. We report significant associations between higher serum cholesterol (CHOL) and high-density lipoprotein levels and higher fractional anisotropy in 403 young adults (23.8 ± 2.4years) scanned with diffusion imaging and anatomic magnetic resonance imaging at 4Tesla. By fitting a multi-locus genetic model within white matter areas associated with CHOL, we found that a set of 18 cholesterol-related, single-nucleotide polymorphisms implicated in Alzheimer's disease risk predicted fractional anisotropy. We focused on the single-nucleotide polymorphism with the largest individual effects, CETP (rs5882), and found that increased G-allele dosage was associated with higher fractional anisotropy and lower radial and mean diffusivities in voxel-wise analyses of the whole brain. A follow-up analysis detected white matter associations with rs5882 in the opposite direction in 78 older individuals (74.3 ± 7.3years). Cholesterol levels may influence white matter integrity, and cholesterol-related genes may exert age-dependent effects on the brain.

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4 citations in Web of Science®

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ID Code: 85856
Item Type: Journal Article
Refereed: No
Keywords: Aging, Brain structure, Cholesterol, Development, DTI, Imaging genetics
DOI: 10.1016/j.neurobiolaging.2014.05.024
ISSN: 1558-1497
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2014 Elsevier Inc
Deposited On: 28 Sep 2015 03:34
Last Modified: 30 Sep 2015 03:39

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