Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
24997672
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
2014 Nov
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 NOTE
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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