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.
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PMID
23303482
TITLE
ANKK1, TTC12, and NCAM1 polymorphisms and heroin dependence: importance of considering drug exposure.
ABSTRACT
CONTEXT NlmCategory: BACKGROUND
The genetic contribution to liability for opioid dependence is well established; identification of the responsible genes has proved challenging.
OBJECTIVE NlmCategory: OBJECTIVE
To examine association of 1430 candidate gene single-nucleotide polymorphisms (SNPs) with heroin dependence, reporting here only the 71 SNPs in the chromosome 11 gene cluster (NCAM1, TTC12, ANKK1, DRD2) that include the strongest observed associations.
DESIGN NlmCategory: METHODS
Case-control genetic association study that included 2 control groups (lacking an established optimal control group).
SETTING NlmCategory: METHODS
Semistructured psychiatric interviews.
PARTICIPANTS NlmCategory: METHODS
A total of 1459 Australian cases ascertained from opioid replacement therapy clinics, 531 neighborhood controls ascertained from economically disadvantaged areas near opioid replacement therapy clinics, and 1495 unrelated Australian Twin Registry controls not dependent on alcohol or illicit drugs selected from a twin and family sample.
MAIN OUTCOME MEASURE NlmCategory: METHODS
Lifetime heroin dependence.
RESULTS NlmCategory: RESULTS
Comparison of cases with Australian Twin Registry controls found minimal evidence of association for all chromosome 11 cluster SNPs (P ≥ .01); a similar comparison with neighborhood controls revealed greater differences (P ≥ 1.8 × 10(-4)). Comparing cases (n = 1459) with the subgroup of neighborhood controls not dependent on illicit drugs (n = 340), 3 SNPs were significantly associated (correcting for multiple testing): ANKK1 SNP rs877138 (most strongly associated; odds ratio = 1.59; 95% CI, 1.32-1.92; P = 9.7 × 10(-7)), ANKK1 SNP rs4938013, and TTC12 SNP rs7130431. A similar pattern of association was observed when comparing illicit drug-dependent (n = 191) and nondependent (n = 340) neighborhood controls, suggesting that liability likely extends to nonopioid illicit drug dependence. Aggregate heroin dependence risk associated with 2 SNPs, rs877138 and rs4492854 (located in NCAM1), varied more than 4-fold (P = 2.7 × 10(-9) for the risk-associated linear trend).
CONCLUSIONS NlmCategory: CONCLUSIONS
Our results provide further evidence of association for chromosome 11 gene cluster SNPs with substance dependence, including extension of liability to illicit drug dependence. Our findings highlight the necessity of considering drug exposure history when selecting control groups for genetic investigations of illicit drug dependence.
DATE PUBLISHED
2013 Mar
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2013/01/11 06:00
pubmed 2013/01/11 06:00
medline 2013/05/03 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, Missouri 63110, USA. nelsone@wustl.edu
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
Saccone NL Saccone Nancy L NL
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: 70
ISSUE: 3
TITLE: JAMA psychiatry
ISOABBREVIATION: JAMA Psychiatry
YEAR: 2013
MONTH: Mar
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2168-6238
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: JAMA Psychiatry
COUNTRY: United States
ISSNLINKING: 2168-622X
NLMUNIQUEID: 101589550
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
R01 DA023668 NIDA NIH HHS United States
R01 DA23668 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Antigens, CD56 genetics
Australia genetics
Case-Control Studies genetics
Female genetics
Gene Frequency genetics
Genetic Association Studies genetics
Genetic Predisposition to Disease genetics
Genotype genetics
Heroin Dependence genetics
Humans genetics
Logistic Models genetics
Male genetics
Middle Aged genetics
Polymorphism, Single Nucleotide genetics
Protein-Serine-Threonine Kinases genetics
Proteins genetics
Receptors, Dopamine D2 genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Antigens, CD56
0 NCAM1 protein, human
0 Proteins
0 Receptors, Dopamine D2
0 TTC12 protein, human
EC 2.7.11.1 ANKK1 protein, human
EC 2.7.11.1 Protein-Serine-Threonine Kinases
OTHER ID's
OTHERID SOURCE
NIHMS516034 NLM
PMC3789525 NLM