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PMID
25744370
TITLE
Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
No opioid receptor, mu 1 (OPRM1) gene polymorphisms, including the functional single nucleotide polymorphism (SNP) rs1799971, have been conclusively associated with heroin/other opioid addiction, despite their biological plausibility. We used evidence of polymorphisms altering OPRM1 expression in normal human brain tissue to nominate and then test associations with heroin addiction.
METHODS NlmCategory: METHODS
We tested 103 OPRM1 SNPs for association with OPRM1 messenger RNA expression in prefrontal cortex from 224 European Americans and African Americans of the BrainCloud cohort. We then tested the 16 putative cis-expression quantitative trait loci (cis-eQTL) SNPs for association with heroin addiction in the Urban Health Study and two replication cohorts, totaling 16,729 European Americans, African Americans, and Australians of European ancestry.
RESULTS NlmCategory: RESULTS
Four putative cis-eQTL SNPs were significantly associated with heroin addiction in the Urban Health Study (smallest p = 8.9 × 10(-5)): rs9478495, rs3778150, rs9384169, and rs562859. Rs3778150, located in OPRM1 intron 1, was significantly replicated (p = 6.3 × 10(-5)). Meta-analysis across all case-control cohorts resulted in p = 4.3 × 10(-8): the rs3778150-C allele (frequency = 16%-19%) being associated with increased heroin addiction risk. Importantly, the functional SNP allele rs1799971-A was associated with heroin addiction only in the presence of rs3778150-C (p = 1.48 × 10(-6) for rs1799971-A/rs3778150-C and p = .79 for rs1799971-A/rs3778150-T haplotypes). Lastly, replication was observed for six other intron 1 SNPs that had prior suggestive associations with heroin addiction (smallest p = 2.7 × 10(-8) for rs3823010).
CONCLUSIONS NlmCategory: CONCLUSIONS
Our findings show that common OPRM1 intron 1 SNPs have replicable associations with heroin addiction. The haplotype structure of rs3778150 and nearby SNPs may underlie the inconsistent associations between rs1799971 and heroin addiction.
Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2015 Oct 1
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/10/13
revised 2014/12/18
accepted 2015/01/08
aheadofprint 2015/01/29
entrez 2015/03/07 06:00
pmc-release 2016/10/01 00:00
pubmed 2015/03/07 06:00
medline 2015/03/07 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Hancock DB Hancock Dana B DB Behavioral Health Epidemiology Program, Behavioral Health and Criminal Justice Division, Research Triangle Institute (RTI) International, St. Louis, Missouri.. Electronic address: dhancock@rti.org.
Levy JL Levy Joshua L JL Research Computing Division, RTI International, Research Triangle Park, North Carolina, St. Louis, Missouri.
Gaddis NC Gaddis Nathan C NC Research Computing Division, RTI International, Research Triangle Park, North Carolina, St. Louis, Missouri.
Glasheen C Glasheen Cristie C Behavioral Health Epidemiology Program, Behavioral Health and Criminal Justice Division, Research Triangle Institute (RTI) International, St. Louis, Missouri.
Saccone NL Saccone Nancy L NL Department of Genetics, Washington University in St. Louis, St. Louis, Missouri.
Page GP Page Grier P GP Center for Public Health Genomics, RTI International, Atlanta, Georgia.
Hulse GK Hulse Gary K GK School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia, Australia.
Wildenauer D Wildenauer Dieter D School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia, Australia.
Kelty EA Kelty Erin A EA School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia, Australia.
Schwab SG Schwab Sibylle G SG Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany.; Faculty of Science, Medicine, and Health, University of Wollongong, Wollongong, New South Wales.
Degenhardt L Degenhardt Louisa L National Drug and Alcohol Research Centre, University of New South Wales, Sydney.
Martin NG Martin Nicholas G NG Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland.
Montgomery GW Montgomery Grant W GW Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland.
Attia J Attia John J Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales.; Clinical Research Design, IT and Statistical Support Unit, Hunter Medical Research Institute, Newcastle, New South Wales.
Holliday EG Holliday Elizabeth G EG Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales.; Clinical Research Design, IT and Statistical Support Unit, Hunter Medical Research Institute, Newcastle, New South Wales.
McEvoy M McEvoy Mark M Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales.; Public Health Research Program, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales.
Scott RJ Scott Rodney J RJ Center for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales.; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales.; Division of Genetics, Hunter Area Pathology Service, Newcastle, New South Wales, Australia.
Bierut LJ Bierut Laura J LJ Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri.
Nelson EC Nelson Elliot C EC Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri.
Kral AH Kral Alex H AH Urban Health Program, Behavioral Health and Criminal Justice Division, RTI International, San Francisco, California.
Johnson EO Johnson Eric O EO Fellow Program and Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, North Carolina.
INVESTIGATORS
JOURNAL
VOLUME: 78
ISSUE: 7
TITLE: Biological psychiatry
ISOABBREVIATION: Biol. Psychiatry
YEAR: 2015
MONTH: Oct
DAY: 1
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1873-2402
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Biol Psychiatry
COUNTRY: United States
ISSNLINKING: 0006-3223
NLMUNIQUEID: 0213264
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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GENERAL NOTE
KEYWORDS
KEYWORD
Genetic association study
Heroin
Multiancestry
OPRM1
Opioid
Prefrontal cortex
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS669095 [Available on 10/01/16] NLM
PMC4519434 [Available on 10/01/16] NLM
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