|
|
| PMID |
|
|
| TITLE |
|
| Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure. |
|
| 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. |
| Copyright © 2014 Elsevier Inc. All rights reserved. |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| received |
2013/10/21 |
| revised |
2014/05/21 |
| accepted |
2014/05/26 |
| aheadofprint |
2014/06/02 |
| entrez |
2014/07/07 06:00 |
| pubmed |
2014/07/07 06:00 |
| medline |
2015/10/20 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Warstadt NM |
|
Warstadt |
Nicholus M |
NM |
|
Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. |
| Dennis EL |
|
Dennis |
Emily L |
EL |
|
Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. |
| Jahanshad N |
|
Jahanshad |
Neda |
N |
|
Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. |
| Kohannim O |
|
Kohannim |
Omid |
O |
|
Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA. |
| Nir TM |
|
Nir |
Talia M |
TM |
|
Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. |
| McMahon KL |
|
McMahon |
Katie L |
KL |
|
Centre for Advanced Imaging, University of Queensland, Brisbane, Australia. |
| de Zubicaray GI |
|
de Zubicaray |
Greig I |
GI |
|
School of Psychology, University of Queensland, Brisbane, Australia. |
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Australia. |
| Henders AK |
|
Henders |
Anjali K |
AK |
|
Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Australia. |
| Whitfield JB |
|
Whitfield |
John B |
JB |
|
Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Australia. |
| Jack CR Jr |
|
Jack |
Clifford R |
CR |
|
Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA. |
| Bernstein MA |
|
Bernstein |
Matt A |
MA |
|
Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA. |
| Weiner MW |
|
Weiner |
Michael W |
MW |
|
Department of Radiology and Biomedical Imaging, UCSF School of Medicine, San Francisco, CA, USA; Veteran Affairs Medical Center, San Francisco, CA, USA. |
| Toga AW |
|
Toga |
Arthur W |
AW |
|
Laboratory of Neuro Imaging, Institute for Neuroimaging and Informatics, USC Keck School of Medicine, Los Angeles, CA, USA. |
| Wright MJ |
|
Wright |
Margaret J |
MJ |
|
School of Psychology, University of Queensland, Brisbane, Australia; Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Australia. |
| Thompson PM |
|
Thompson |
Paul M |
PM |
|
Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA; Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA. Electronic address: pthomp@usc.edu. |
|
Alzheimer's Disease Neuroimaging Initiative (ADNI) |
|
|
|
|
|
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 35 |
| ISSUE: 11 |
| TITLE: Neurobiology of aging |
| ISOABBREVIATION: Neurobiol. Aging |
| YEAR: 2014 |
| MONTH: Nov |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1558-1497 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Neurobiol Aging |
| COUNTRY: United States |
| ISSNLINKING: 0197-4580 |
| NLMUNIQUEID: 8100437 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
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|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| 5R01MH094343. |
NIMH NIH HHS |
United States |
| EB007813 |
NIBIB NIH HHS |
United States |
| EB008281 |
NIBIB NIH HHS |
United States |
| EB008432 |
NIBIB NIH HHS |
United States |
| P41 EB015922 |
NIBIB NIH HHS |
United States |
| P41RR013642 |
NCRR NIH HHS |
United States |
| R01 AG040060 |
NIA NIH HHS |
United States |
| R01 EB007813 |
NIBIB NIH HHS |
United States |
| R01 EB008281 |
NIBIB NIH HHS |
United States |
| R01 EB008432 |
NIBIB NIH HHS |
United States |
| R01 HD050735 |
NICHD NIH HHS |
United States |
| R01 HD050735 |
NICHD NIH HHS |
United States |
| R01 MH094343 |
NIMH NIH HHS |
United States |
| RF1 AG041915 |
NIA NIH HHS |
United States |
| T32 MH073526 |
NIMH NIH HHS |
United States |
| T32 MH073526-06 |
NIMH NIH HHS |
United States |
| U01 AG024904 |
NIA NIH HHS |
United States |
| U24 AG021886 |
NIA NIH HHS |
United States |
| U54 EB020403 |
NIBIB NIH HHS |
United States |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
| KEYWORD |
| Aging |
| Brain structure |
| Cholesterol |
| DTI |
| Development |
| Imaging genetics |
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adult |
|
| Aging |
|
| Alleles |
|
| Alzheimer Disease |
genetics |
| Anisotropy |
genetics |
| Cholesterol |
blood |
| Cholesterol Ester Transfer Proteins |
genetics |
| Diffusion Magnetic Resonance Imaging |
genetics |
| Female |
genetics |
| Follow-Up Studies |
genetics |
| Forecasting |
genetics |
| Humans |
genetics |
| Male |
genetics |
| Myelin Sheath |
metabolism |
| Polymorphism, Single Nucleotide |
metabolism |
| Risk |
metabolism |
| White Matter |
pathology |
| Young Adult |
pathology |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
CETP protein, human |
| 0 |
Cholesterol Ester Transfer Proteins |
| 97C5T2UQ7J |
Cholesterol |
|
| OTHER ID's |
|
| OTHERID |
SOURCE |
| NIHMS611906 |
NLM |
| PMC4198330 |
NLM |
|
|
