Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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
25072390
TITLE
Obesity gene NEGR1 associated with white matter integrity in healthy young adults.
ABSTRACT
Obesity is a crucial public health issue in developed countries, with implications for cardiovascular and brain health as we age. A number of commonly-carried genetic variants are associated with obesity. Here we aim to see whether variants in obesity-associated genes--NEGR1, FTO, MTCH2, MC4R, LRRN6C, MAP2K5, FAIM2, SEC16B, ETV5, BDNF-AS, ATXN2L, ATP2A1, KCTD15, and TNN13K--are associated with white matter microstructural properties, assessed by high angular resolution diffusion imaging (HARDI) in young healthy adults between 20 and 30 years of age from the Queensland Twin Imaging study (QTIM). We began with a multi-locus approach testing how a number of common genetic risk factors for obesity at the single nucleotide polymorphism (SNP) level may jointly influence white matter integrity throughout the brain and found a wide spread genetic effect. Risk allele rs2815752 in NEGR1 was most associated with lower white matter integrity across a substantial portion of the brain. Across the area of significance in the bilateral posterior corona radiata, each additional copy of the risk allele was associated with a 2.2% lower average FA. This is the first study to find an association between an obesity risk gene and differences in white matter integrity. As our subjects were young and healthy, our results suggest that NEGR1 has effects on brain structure independent of its effect on obesity.
Copyright © 2014. Published by Elsevier Inc.
DATE PUBLISHED
2014 Nov 15
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/04/12
revised 2014/06/23
accepted 2014/07/22
aheadofprint 2014/07/27
entrez 2014/07/30 06:00
pubmed 2014/07/30 06:00
medline 2015/08/04 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Dennis EL Dennis Emily L EL Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
Jahanshad N Jahanshad Neda N Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
Braskie MN Braskie Meredith N MN Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
Warstadt NM Warstadt Nicholus M NM Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
Hibar DP Hibar Derrek P DP Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
Kohannim O Kohannim Omid O Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Nir TM Nir Talia M TM Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
McMahon KL McMahon Katie L KL Center for Advanced Imaging, Univ. 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, Brisbane, Australia.
Martin NG Martin Nicholas G NG Queensland Institute of Medical Research, Brisbane, Australia.
Toga AW Toga Arthur W AW Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
Wright MJ Wright Margaret J MJ School of Psychology, University of Queensland, Brisbane, Australia; Queensland Institute of Medical Research, Brisbane, Australia.
Thompson PM Thompson Paul M PM Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA; Departments of Neurology, Psychiatry, Radiology, Engineering, and Ophthalmology, Keck School of Medicine of USC, Los Angeles, CA, USA. Electronic address: pthomp@usc.edu.
INVESTIGATORS
JOURNAL
VOLUME: 102 Pt 2
ISSUE:
TITLE: NeuroImage
ISOABBREVIATION: Neuroimage
YEAR: 2014
MONTH: Nov
DAY: 15
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1095-9572
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Neuroimage
COUNTRY: United States
ISSNLINKING: 1053-8119
NLMUNIQUEID: 9215515
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
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
P41 RR013642 NCRR NIH HHS United States
R01 AG040060 NIA NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
RF1 AG041915 NIA NIH HHS United States
T32MH073526-06 NIMH NIH HHS United States
U54 EB020403 NIBIB NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
HARDI
SNP
diffusion tensor imaging
genetics
multi-locus
obesity
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Brain physiology
Cell Adhesion Molecules, Neuronal genetics
Diffusion Tensor Imaging genetics
Female genetics
GPI-Linked Proteins genetics
Genetic Variation genetics
Genome-Wide Association Study genetics
Humans genetics
Male genetics
Obesity genetics
Polymorphism, Single Nucleotide genetics
White Matter physiology
Young Adult physiology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Cell Adhesion Molecules, Neuronal
0 GPI-Linked Proteins
0 NEGR1 protein, human
OTHER ID's
OTHERID SOURCE
NIHMS646698 NLM
PMC4269485 NLM
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