Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
18433502
TITLE
Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Variation in response to the hedonic and adverse effects of a substance is in part an inherited factor that may influence its use, abuse and dependence. The mu opioid receptor is the primary site of action for opiates and individuals with polymorphisms in this receptor appear to have variation in the CNS effects of opiates. Several studies have suggested that this receptor may also mediate some of the effects of non-opioid drugs, such as alcohol. The purpose of this study was to investigate associations between 13 single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) with self-reported responses to alcohol, an endophenotype associated with the development of alcohol dependence, in American Indians living on eight contiguous reservations.
METHODS NlmCategory: METHODS
Each participant gave a blood sample and completed a structured diagnostic interview. Additionally, response to alcohol was indexed using the expectation version of the subjective high assessment scale (SHAS-E). SNPs were genotyped in 251 participants and data analyses were conducted using SOLAR.
RESULTS NlmCategory: RESULTS
The estimated heritability (h2) for the SHAS-E phenotypes ranged from 0.01 to 0.28. Endorsing the expectation of a more intense response on one or more of the following items from the SHAS-E: buzzed, clumsy, dizzy, drunk, effects, high, nausea, sleepy, talkative, terrible, and/or uncomfortable after imbibing 2-3 drinks was significantly associated with having at least one minor allele for at least one of 7 SNPs (p < 0.01) in the OPRM1 receptor gene.
CONCLUSION NlmCategory: CONCLUSIONS
These studies provide data to suggest that the minor allele, for most of the polymorphisms in the OPRM1 receptor gene investigated, was found to be associated with a more intense, and/or more adverse, response to alcohol, traits that are significantly correlated with lowered quantity of alcohol consumption and less susceptibility to dependence in this Indian population. These data further suggest that making conclusions on the role of the mu opiod receptor gene in the development of alcohol dependence may be limited if only one polymorphism in the gene is evaluated in isolation.
DATE PUBLISHED
2008
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2007/11/30
accepted 2008/04/23
aheadofprint 2008/04/23
pubmed 2008/04/25 09:00
medline 2008/05/22 09:00
entrez 2008/04/25 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Ehlers CL Ehlers Cindy L CL Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA. cindye@scripps.edu
Lind PA Lind Penelope A PA
Wilhelmsen KC Wilhelmsen Kirk C KC
INVESTIGATORS
JOURNAL
VOLUME: 9
ISSUE:
TITLE: BMC medical genetics
ISOABBREVIATION: BMC Med. Genet.
YEAR: 2008
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1471-2350
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: BMC Med Genet
COUNTRY: England
ISSNLINKING: 1471-2350
NLMUNIQUEID: 100968552
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
Cites Alcohol Clin Exp Res. 2004 Dec;28(12):1789-95 15608594
Cites Bioinformatics. 2005 Jan 15;21(2):263-5 15297300
Cites Am J Med Genet B Neuropsychiatr Genet. 2005 Feb 5;133B(1):105-9 15558714
Cites Trends Mol Med. 2005 Feb;11(2):82-9 15694871
Cites Psychiatr Genet. 2005 Mar;15(1):71-5 15722961
Cites Anesthesiology. 2005 Mar;102(3):522-30 15731588
Cites Psychiatr Genet. 2005 Jun;15(2):101-7 15900224
Cites Trends Pharmacol Sci. 2005 Jun;26(6):311-7 15925706
Cites Bioinformatics. 2005 Aug 15;21(16):3445-7 15947021
Cites J Biol Chem. 2005 Sep 23;280(38):32618-24 16046395
Cites Alcohol Clin Exp Res. 2005 Nov;29(11):1976-82 16340454
Cites Clin Pharmacol Ther. 2006 Jan;79(1):72-89 16413243
Cites Hum Mol Genet. 2006 Mar 15;15(6):807-19 16476706
Cites BMC Med Genet. 2006;7:9 16472381
Cites Clin Pharmacol Ther. 2006 Apr;79(4):316-24 16580900
Cites JAMA. 2006 May 3;295(17):2003-17 16670409
Cites Pharmacogenomics J. 2006 May-Jun;6(3):179-88 16402083
Cites Pharmacogenomics J. 2006 May-Jun;6(3):200-10 16415919
Cites Drug Alcohol Depend. 2006 Jul 27;83(3):262-8 16387451
Cites Pharmacogenet Genomics. 2006 Sep;16(9):625-36 16906017
Cites Anesth Analg. 2006 Oct;103(4):1011-7 17000822
Cites Alcohol Clin Exp Res. 2006 Nov;30(11):1856-65 17067349
Cites Clin Pharmacol Ther. 2007 Mar;81(3):429-44 17339873
Cites Genes Brain Behav. 2007 Mar;6(2):184-91 16764678
Cites Psychiatr Genet. 2007 Jun;17(3):171-6 17417061
Cites Biol Psychiatry. 2007 Jun 1;61(11):1244-51 17157823
Cites Arch Gen Psychiatry. 2007 Sep;64(9):1069-77 17768272
Cites Am J Med Genet B Neuropsychiatr Genet. 2007 Oct 5;144B(7):877-84 17503481
Cites Arch Gen Psychiatry. 2008 Feb;65(2):135-44 18250251
Cites Alcohol Clin Exp Res. 2007 Apr;31(4):555-63 17374034
Cites Alcohol Clin Exp Res. 1995 Jun;19(3):617-22 7573783
Cites Arch Gen Psychiatry. 1996 Mar;53(3):202-10 8611056
Cites Neurochem Res. 1996 Nov;21(11):1469-88 8947936
Cites Psychopharmacology (Berl). 1997 Jan;129(2):99-111 9040115
Cites Alcohol Alcohol. 1997 Mar-Apr;32(2):129-32 9105506
Cites Am J Psychiatry. 1997 Jul;154(7):983-8 9210750
Cites J Pain Symptom Manage. 1997 Sep;14(3):157-67 9291702
Cites Neuropsychopharmacology. 1998 Apr;18(4):282-92 9509496
Cites Am J Hum Genet. 1998 May;62(5):1198-211 9545414
Cites Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9608-13 9689128
Cites Biol Psychiatry. 1999 Mar 15;45(6):776-87 10188009
Cites Alcohol Clin Exp Res. 1999 May;23(5):759-69 10371393
Cites Ann N Y Acad Sci. 2004 Oct;1025:316-24 15542732
Cites Alcohol Clin Exp Res. 2004 Oct;28(10):1481-6 15597079
Cites Am J Psychiatry. 1999 Nov;156(11):1758-64 10553740
Cites Psychol Med. 1999 Sep;29(5):1069-81 10576299
Cites Nat Med. 2000 Jun;6(6):637-41 10835679
Cites Alcohol Alcohol. 2000 May-Jun;35(3):242-8 10869242
Cites Hum Mol Genet. 2000 Nov 22;9(19):2895-908 11092766
Cites Eur J Pharmacol. 2000 Dec 27;410(2-3):243-248 11134673
Cites Alcohol Clin Exp Res. 2001 May;25(5):672-9 11371716
Cites Biol Psychiatry. 2001 Jul 15;50(2):129-36 11526994
Cites J Stud Alcohol. 2001 Sep;62(5):562-70 11702795
Cites Alcohol Clin Exp Res. 2001 Nov;25(11):1634-47 11707638
Cites Psychiatry Res. 2001 Dec 15;105(1-2):67-78 11740976
Cites Neuropsychopharmacology. 2002 Jan;26(1):106-14 11751037
Cites Pharmacogenetics. 2002 Jan;12(1):3-9 11773859
Cites Public Health Rep. 2001;116 Suppl 1:216-22 11889287
Cites Hum Mutat. 2002 Apr;19(4):459-60 11933204
Cites Anesthesiology. 2002 Oct;97(4):814-9 12357145
Cites Am J Psychiatry. 2003 Jan;160(1):41-6 12505800
Cites Arch Gen Psychiatry. 2003 Jan;60(1):92-9 12511176
Cites Clin Pharmacol Ther. 2003 Jan;73(1):107-21 12545149
Cites Am J Med Genet B Neuropsychiatr Genet. 2003 Apr 1;118B(1):60-5 12627468
Cites Anesthesiology. 2003 Jun;98(6):1415-21 12766651
Cites Alcohol Alcohol. 2003 Jul-Aug;38(4):332-8 12814900
Cites Am J Med Genet B Neuropsychiatr Genet. 2003 Jul 1;120B(1):97-108 12815747
Cites Neuropsychopharmacology. 2003 Aug;28(8):1546-52 12813472
Cites Alcohol Clin Exp Res. 2003 Jul;27(7):1041-7 12878909
Cites Alcohol Clin Exp Res. 2003 Jul;27(7):1142-9 12878920
Cites Psychiatr Genet. 2003 Sep;13(3):169-73 12960749
Cites Anesthesiology. 2004 Jan;100(1):120-33 14695733
Cites Am J Psychiatry. 2004 Jul;161(7):1204-10 15229052
Cites Alcohol Clin Exp Res. 2004 Jul;28(7):986-90 15252283
Cites Am J Med Genet B Neuropsychiatr Genet. 2004 Aug 15;129B(1):110-5 15274051
Cites Acta Anaesthesiol Scand. 2004 Nov;48(10):1232-9 15504181
Cites Arch Gen Psychiatry. 1984 Sep;41(9):879-84 6466047
Cites J Stud Alcohol. 1985 Jul;46(4):289-97 4033129
Cites JAMA. 1985 Nov 8;254(18):2614-7 4057470
Cites J Stud Alcohol. 1986 Jul;47(4):297-304 3747531
Cites J Stud Alcohol. 1988 Sep;49(5):430-5 3216646
Cites Alcohol Clin Exp Res. 1989 Apr;13(2):252-7 2658666
Cites Psychol Bull. 1990 Nov;108(3):383-402 2270234
Cites J Stud Alcohol. 1991 Sep;52(5):464-9 1943102
Cites Am J Psychiatry. 1992 Nov;149(11):1534-8 1415821
Cites Alcohol Clin Exp Res. 1992 Oct;16(5):991-5 1443441
Cites Arch Gen Psychiatry. 1992 Nov;49(11):876-80 1345133
Cites Arch Gen Psychiatry. 1992 Nov;49(11):881-7 1444726
Cites Biol Psychiatry. 1993 Jul 1-15;34(1-2):91-9 8373942
Cites FEBS Lett. 1994 Jan 31;338(2):217-22 7905839
Cites J Stud Alcohol. 1994 Jan;55(1):5-17 8189726
Cites J Stud Alcohol. 1994 Mar;55(2):149-58 8189735
Cites J Stud Alcohol. 1994 Mar;55(2):207-13 8189741
Cites Science. 1994 Sep 30;265(5181):2037-48 8091226
GRANTS
GRANTID AGENCY COUNTRY
5R37 AA010201 NIAAA NIH HHS United States
R37 AA010201 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Alcoholism genetics
Alleles genetics
Female genetics
Genetic Markers genetics
Genetic Variation genetics
Humans genetics
Indians, North American genetics
Male genetics
Polymorphism, Single Nucleotide genetics
Receptors, Opioid, mu genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Genetic Markers
0 OPRM1 protein, human
0 Receptors, Opioid, mu
OTHER ID's
OTHERID SOURCE
PMC2386778 NLM