RGD Reference Report - Association of variants in MANEA with cocaine-related behaviors. - Rat Genome Database

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Association of variants in MANEA with cocaine-related behaviors.

Authors: Farrer, Lindsay A  Kranzler, Henry R  Yu, Yi  Weiss, Roger D  Brady, Kathleen T  Anton, Raymond  Cubells, Joseph F  Gelernter, Joel 
Citation: Farrer LA, etal., Arch Gen Psychiatry. 2009 Mar;66(3):267-74. doi: 10.1001/archgenpsychiatry.2008.538.
RGD ID: 401851915
Pubmed: PMID:19255376   (View Abstract at PubMed)
PMCID: PMC2758158   (View Article at PubMed Central)
DOI: DOI:10.1001/archgenpsychiatry.2008.538   (Journal Full-text)


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.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MANEAHumancocaine dependence susceptibilityIAGP DNA:SNPs:multipleRGD 
ManeaRatcocaine dependence susceptibilityISOMANEA (Homo sapiens)DNA:SNPs:multipleRGD 
ManeaMousecocaine dependence susceptibilityISOMANEA (Homo sapiens)DNA:SNPs:multipleRGD 
MANEAHumanParanoid Disorders susceptibilityIAGP associated with cocaine dependence and DNA:SNPs:multipleRGD 
ManeaRatParanoid Disorders susceptibilityISOMANEA (Homo sapiens)associated with cocaine dependence and DNA:SNPs:multipleRGD 
ManeaMouseParanoid Disorders susceptibilityISOMANEA (Homo sapiens)associated with cocaine dependence and DNA:SNPs:multipleRGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MANEAHumanAddictive cocaine use susceptibilityIAGP  RGD 
MANEAHumanParanoia susceptibilityIAGP DNA:SNPs:multipleRGD 
Objects Annotated

Genes (Rattus norvegicus)
Manea  (mannosidase, endo-alpha)

Genes (Mus musculus)
Manea  (mannosidase, endo-alpha)

Genes (Homo sapiens)
MANEA  (mannosidase endo-alpha)


Additional Information