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

Roussotte, Florence F., Jahanshad, Neda, Hibar, Derrek P., Sowell, Elizabeth R., Kohannim, Omid, Barysheva, Marina, Hansell, Narelle K., McMahon, Katie L., de Zubicaray, Greig I., Montgomery, Grant W., Martin, Nicholas G., Wright, Margaret J., Toga, Arthur W., Jack Jr, Clifford R., Weiner, Michael W., Thompson, Paul M. and ADNI (2014) 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. Human Brain Mapping, 35 4: 1226-1236. doi:10.1002/hbm.22247

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Author Roussotte, Florence F.
Jahanshad, Neda
Hibar, Derrek P.
Sowell, Elizabeth R.
Kohannim, Omid
Barysheva, Marina
Hansell, Narelle K.
McMahon, Katie L.
de Zubicaray, Greig I.
Montgomery, Grant W.
Martin, Nicholas G.
Wright, Margaret J.
Toga, Arthur W.
Jack Jr, Clifford R.
Weiner, Michael W.
Thompson, Paul M.
ADNI
Total Author Count Override 17
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
Formatted 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
Journal name Human Brain Mapping   Check publisher's open access policy
ISSN 1065-9471
1097-0193
Publication date 2014-04
Year available 2013
Sub-type Article (original research)
DOI 10.1002/hbm.22247
Open Access Status File (Author Post-print)
Volume 35
Issue 4
Start page 1226
End page 1236
Total pages 11
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2014
Language eng
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.
Keyword Drug addiction
Genetics
Neurodegeneration
Neuroimaging
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 21 February 2013

 
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Created: Wed, 20 Mar 2013, 09:18:54 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging