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Arch Gen Psychiatry. 2009 Mar;66(3):267-74. doi: 10.1001/archgenpsychiatry.2008.538.

Association of variants in MANEA with cocaine-related behaviors.

Author information

  • 1Genetics Program, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA. farrer@bu.edu

Abstract

CONTEXT:

Cocaine dependence (CD) and related behaviors are highly heritable, but no genetic association has been consistently demonstrated. A recent genome-wide study of drug dependence identified an association between cocaine-induced paranoia (CIP) and a single-nucleotide polymorphism (SNP) in the alpha-endomannosidase (MANEA) locus in a family-based sample of European Americans and African Americans.

OBJECTIVE:

To conduct a comprehensive genetic association study of the MANEA locus with CD and CIP.

DESIGN:

Genome-wide association study.

SETTING:

Four university hospitals.

PARTICIPANTS:

A total of 3992 individuals from 2 family-based and 2 case-control samples.

INTERVENTION:

Participants were classified as having CD or CIP or as a control using the Semi-Structured Assessment for Drug Dependence and Alcoholism. They were genotyped for 11 SNPs spanning MANEA and its surrounding region.

MAIN OUTCOME MEASURE:

Association of CD and CIP with individual SNPs and haplotypes.

RESULTS:

Cocaine-induced paranoia was associated with 6 SNPs in the European American families and 9 SNPs in the African American families. The strongest evidence in the total sample of families was observed in 3 markers located in the promoter and 3' untranslated regions (P < .001). The association of MANEA SNPs with CD in both family samples was much weaker. In the African American case-control sample, multiple markers were significantly associated with CIP and CD; CIP and CD were also significantly associated with a 2-SNP haplotype in the European American case-control sample. The A allele of the 3' untranslated region SNP rs9387522 was associated with increased risk of CIP in all 4 data sets.

CONCLUSIONS:

Our findings suggest that CD and associated behaviors may involve biological pathways not typically thought to be associated with brain metabolism.

PMID:
19255376
[PubMed - indexed for MEDLINE]
PMCID:
PMC2758158
Free PMC Article
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