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
22500942
TITLE
Association of OPRD1 polymorphisms with heroin dependence in a large case-control series.
ABSTRACT
Genes encoding the opioid receptors (OPRM1, OPRD1 and OPRK1) are obvious candidates for involvement in risk for heroin dependence. Prior association studies commonly had samples of modest size, included limited single nucleotide polymorphism (SNP) coverage of these genes and yielded inconsistent results. Participants for the current investigation included 1459 heroin-dependent cases ascertained from maintenance clinics in New South Wales, Australia, 1495 unrelated individuals selected from an Australian sample of twins and siblings as not meeting DSM-IV criteria for lifetime alcohol or illicit drug dependence (non-dependent controls) and 531 controls ascertained from economically disadvantaged neighborhoods in proximity to the maintenance clinics. A total of 136 OPRM1, OPRD1 and OPRK1 SNPs were genotyped in this sample. After controlling for admixture with principal components analysis, our comparison of cases to non-dependent controls found four OPRD1 SNPs in fairly high linkage disequilibrium for which adjusted P values remained significant (e.g. rs2236857; OR 1.25; P=2.95×10(-4) ) replicating a previously reported association. A post hoc analysis revealed that the two SNP (rs2236857 and rs581111) GA haplotype in OPRD1 is associated with greater risk (OR 1.68; P=1.41×10(-5) ). No OPRM1 or OPRK1 SNPs reached more than nominal significance. Comparisons of cases to neighborhood controls reached only nominal significance. Our results replicate a prior report providing strong evidence implicating OPRD1 SNPs and, in particular, the two SNP (rs2236857 and rs581111) GA haplotype in liability for heroin dependence. Support was not found for similar association involving either OPRM1 or OPRK1 SNPs.
2012 The Authors, Addiction Biology 2012 Society for the Study of Addiction.
DATE PUBLISHED
2014 Jan
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2012/04/13
entrez 2012/04/17 06:00
pubmed 2012/04/17 06:00
medline 2014/08/19 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Nelson EC Nelson Elliot C EC Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA Queensland Institute of Medical Research, Australia National Drug and Alcohol Research Centre, University of New South Wales, Australia Burnet Institute, Centre for Health Policy, Programs and Economics, School of Population Health, University of Melbourne, Australia.
Lynskey MT Lynskey Michael T MT
Heath AC Heath Andrew C AC
Wray N Wray Naomi N
Agrawal A Agrawal Arpana A
Shand FL Shand Fiona L FL
Henders AK Henders Anjali K AK
Wallace L Wallace Leanne L
Todorov AA Todorov Alexandre A AA
Schrage AJ Schrage Andrew J AJ
Madden PA Madden Pamela A F PA
Degenhardt L Degenhardt Louisa L
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
INVESTIGATORS
JOURNAL
VOLUME: 19
ISSUE: 1
TITLE: Addiction biology
ISOABBREVIATION: Addict Biol
YEAR: 2014
MONTH: Jan
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1369-1600
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Addict Biol
COUNTRY: United States
ISSNLINKING: 1355-6215
NLMUNIQUEID: 9604935
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
K05 AA017688 NIAAA NIH HHS United States
R01 DA017305 NIDA NIH HHS United States
R01 DA017305 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
Association study
OPRD1
OPRK1
OPRM1
case-control
heroin dependence
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Case-Control Studies
Control Groups
Female
Genetic Association Studies
Genetic Predisposition to Disease genetics
HapMap Project genetics
Haplotypes genetics
Heroin Dependence genetics
Humans genetics
Linkage Disequilibrium genetics
Logistic Models genetics
Male genetics
Middle Aged genetics
New South Wales genetics
Polymorphism, Single Nucleotide genetics
Principal Component Analysis genetics
Receptors, Opioid genetics
Receptors, Opioid, delta genetics
Twins genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 OPRD1 protein, human
0 Receptors, Opioid
0 Receptors, Opioid, delta
OTHER ID's
OTHERID SOURCE
NIHMS387380 NLM
PMC3867542 NLM