This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Psychiatry  • Psychiatry, Other  • Public Health  • Substance Abuse/ Alcoholism  • Genetics  • Genetics, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

Lindsay A. Farrer, PhD; Henry R. Kranzler, MD; Yi Yu, MSc; Roger D. Weiss, MD; Kathleen T. Brady, MD, PhD; Raymond Anton, MD; Joseph F. Cubells, MD, PhD; Joel Gelernter, MD

Arch Gen Psychiatry. 2009;66(3):267-274.

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 -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.

Author Affiliations: Departments of Neurology, Genetics & Genomics, Epidemiology, and Biostatistics (Dr Farrer), and Medicine, Genetics Program (Drs Farrer and Yu), Boston University Schools of Medicine and Public Health, Boston, Massachusetts; Department of Psychiatry, University of Connecticut School of Medicine, Farmington (Dr Kranzler); Alcohol and Drug Abuse Treatment Program, McLean Hospital, Belmont, Massachusetts (Dr Weiss); Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston (Drs Brady and Anton); Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia (Dr Cubells); Department of Psychiatry, Division of Human Genetics, and Departments of Neurobiology and Genetics, Yale University School of Medicine, New Haven, Connecticut; and VA Connecticut Healthcare System, West Haven (Dr Gelernter).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?