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.
authors: 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.
authors: Florence F
authors: FF
authors: Roussotte
authors: Neda
authors: N
authors: Jahanshad
authors: Derrek P
authors: DP
authors: Hibar
authors: Elizabeth R
authors: ER
authors: Sowell
authors: Omid
authors: O
authors: Kohannim
authors: Marina
authors: M
authors: Barysheva
authors: Narelle K
authors: NK
authors: Hansell
authors: Katie L
authors: KL
authors: McMahon
authors: Greig I
authors: GI
authors: de Zubicaray
authors: Grant W
authors: GW
authors: Montgomery
authors: Nicholas G
authors: NG
authors: Martin
authors: Margaret J
authors: MJ
authors: Wright
authors: Arthur W
authors: AW
authors: Toga
authors: Clifford R
authors: CR
authors: Jack
authors: Michael W
authors: MW
authors: Weiner
authors: Paul M
authors: PM
authors: Thompson
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics / Q000473:pathology*; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics / Q000473:pathology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000235:genetics / Q000473:pathology*; D016208:Databases, Factual; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015810:Linkage Disequilibrium; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D017465:Receptors, Opioid, delta / Q000235:genetics*; D018433:Twin Studies as Topic; D055815:Young Adult
chemical_list: D015415:Biomarkers; C529706:OPRD1 protein, human; D017465:Receptors, Opioid, delta
keywords: drug addiction; genetics; neurodegeneration; neuroimaging; opiates