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

Warstadt, Nicholus M., Dennis, Emily L., Jahanshad, Neda, Kohannim, Omid, Nir, Talia M., McMahon, Katie L., de Zubicaray, Greig I., Montgomery, Grant W., Henders, Anjali K., Martin, Nicholas G., Whitfield, John B., Jack, Clifford R. Jr., Bernstein, Matt A., Weiner, Michael W., Toga, Arthur W., Wright, Margaret J., Thompson, Paul M. and for the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (2014) Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure. Neurobiology of Aging, 35 11: 2504-2513. doi:10.1016/j.neurobiolaging.2014.05.024

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Author Warstadt, Nicholus M.
Dennis, Emily L.
Jahanshad, Neda
Kohannim, Omid
Nir, Talia M.
McMahon, Katie L.
de Zubicaray, Greig I.
Montgomery, Grant W.
Henders, Anjali K.
Martin, Nicholas G.
Whitfield, John B.
Jack, Clifford R. Jr.
Bernstein, Matt A.
Weiner, Michael W.
Toga, Arthur W.
Wright, Margaret J.
Thompson, Paul M.
for the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Total Author Count Override 17
Title Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure
Formatted title
Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure
Journal name Neurobiology of Aging   Check publisher's open access policy
ISSN 0197-4580
1558-1497
Publication date 2014-11
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.neurobiolaging.2014.05.024
Open Access Status
Volume 35
Issue 11
Start page 2504
End page 2513
Total pages 10
Place of publication Philadelphia, United States
Publisher Elsevier
Collection year 2015
Language eng
Formatted 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 ± 2.4 years) scanned with diffusion imaging and anatomic magnetic resonance imaging at 4 Tesla. 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 ± 7.3 years). Cholesterol levels may influence white matter integrity, and cholesterol-related genes may exert age-dependent effects on the brain.
Keyword Brain structure
DTI
Imaging genetics
Cholesterol
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print: 1 June 2014.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Psychology Publications
Centre for Advanced Imaging Publications
 
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Created: Tue, 24 Jun 2014, 11:03:59 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging