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
23427138
TITLE
A commonly carried genetic variant in the delta opioid receptor gene, OPRD1, is associated with smaller regional brain volumes: replication in elderly and young populations.
ABSTRACT
Delta opioid receptors are implicated in a variety of psychiatric and neurological disorders. These receptors play a key role in the reinforcing properties of drugs of abuse, and polymorphisms in OPRD1 (the gene encoding delta opioid receptors) are associated with drug addiction. Delta opioid receptors are also involved in protecting neurons against hypoxic and ischemic stress. Here, we first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative. We hypothesized that common variants in OPRD1 would be associated with differences in brain structure, particularly in regions relevant to addictive and neurodegenerative disorders. One very common variant (rs678849) predicted differences in regional brain volumes. We replicated the association of this single-nucleotide polymorphism with regional tissue volumes in a large sample of young participants in the Queensland Twin Imaging study. Although the same allele was associated with reduced volumes in both cohorts, the brain regions affected differed between the two samples. In healthy elderly, exploratory analyses suggested that the genotype associated with reduced brain volumes in both cohorts may also predict cerebrospinal fluid levels of neurodegenerative biomarkers, but this requires confirmation. If opiate receptor genetic variants are related to individual differences in brain structure, genotyping of these variants may be helpful when designing clinical trials targeting delta opioid receptors to treat neurological disorders.
Copyright 2013 Wiley Periodicals, Inc.
DATE PUBLISHED
2014 Apr
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/07/23
revised 2012/11/01
accepted 2012/11/30
aheadofprint 2013/02/21
entrez 2013/02/22 06:00
pubmed 2013/02/22 06:00
medline 2014/12/15 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Roussotte FF Roussotte Florence F FF Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Pediatrics, Developmental Cognitive Neuroimaging Laboratory (DCNL), University of Southern California, Los Angeles, California.
Jahanshad N Jahanshad Neda N
Hibar DP Hibar Derrek P DP
Sowell ER Sowell Elizabeth R ER
Kohannim O Kohannim Omid O
Barysheva M Barysheva Marina M
Hansell NK Hansell Narelle K NK
McMahon KL McMahon Katie L KL
de Zubicaray GI de Zubicaray Greig I GI
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Wright MJ Wright Margaret J MJ
Toga AW Toga Arthur W AW
Jack CR Jr Jack Clifford R CR
Weiner MW Weiner Michael W MW
Thompson PM Thompson Paul M PM
ADNI
INVESTIGATORS
JOURNAL
VOLUME: 35
ISSUE: 4
TITLE: Human brain mapping
ISOABBREVIATION: Hum Brain Mapp
YEAR: 2014
MONTH: Apr
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1097-0193
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Brain Mapp
COUNTRY: United States
ISSNLINKING: 1065-9471
NLMUNIQUEID: 9419065
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
1F30AG041681 NIA NIH HHS United States
F30 AG041681 NIA NIH HHS United States
K01 AG030514 NIA NIH HHS United States
K01 AG030514 NIA NIH HHS United States
P30 AG010129 NIA NIH HHS United States
R01 AG040060 NIA NIH HHS United States
R01 AG040060 NIA NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01 MH097268 NIMH NIH HHS United States
R01 MH097268 NIMH NIH HHS United States
U01 AG024904 NIA NIH HHS United States
U01 AG024904 NIA NIH HHS United States
U24 AG021886 NIA NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
drug addiction
genetics
neurodegeneration
neuroimaging
opiates
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Aged
Aging pathology
Alzheimer Disease pathology
Biomarkers cerebrospinal fluid
Brain pathology
Databases, Factual pathology
Female pathology
Genotyping Techniques pathology
Humans pathology
Image Processing, Computer-Assisted pathology
Linkage Disequilibrium pathology
Magnetic Resonance Imaging pathology
Male pathology
Mild Cognitive Impairment pathology
Organ Size pathology
Polymorphism, Single Nucleotide pathology
Receptors, Opioid, delta genetics
Twin Studies as Topic genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Biomarkers
0 OPRD1 protein, human
0 Receptors, Opioid, delta
OTHER ID's
OTHERID SOURCE
NIHMS504323 NLM
PMC4046708 NLM