Journal article
Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence
Molecular psychiatry, Vol.14(5), pp.501-510
2009
DOI: 10.1038/mp.2008.42
PMCID: PMC4381434
PMID: 18414406
Abstract
Alcohol dependence frequently co-occurs with cigarette smoking, another common addictive behavior. Evidence from genetic studies demonstrates that alcohol dependence and smoking cluster in families and have shared genetic vulnerability. Recently a candidate gene study in nicotine dependent cases and nondependent smoking controls reported strong associations between a missense mutation (rs16969968) in exon 5 of the CHRNA5 gene and a variant in the 3′-UTR of the CHRNA3 gene and nicotine dependence. In this study we performed a comprehensive association analysis of the CHRNA5–CHRNA3–CHRNB4 gene cluster in the Collaborative Study on the Genetics of Alcoholism (COGA) families to investigate the role of genetic variants in risk for alcohol dependence. Using the family-based association test, we observed that a different group of polymorphisms, spanning CHRNA5-CHRNA3, demonstrate association with alcohol dependence defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) criteria. Using logistic regression we replicated this finding in an independent case-control series from the family study of cocaine dependence. These variants show low linkage disequilibrium with the SNPs previously reported to be associated with nicotine dependence and therefore represent an independent observation. Functional studies in human brain reveal that the variants associated with alcohol dependence are also associated with altered steady-state levels of CHRNA5 mRNA.
Details
- Title: Subtitle
- Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence
- Creators
- Jc WangR GruczaC CruchagaA L HinrichsS BertelsenJ P BuddeL FoxE GoldsteinO ReyesN SacconeS SacconeX XueiK BucholzS KupermanJ Nurnberger JrJ P RiceM SchuckitJ TischfieldV HesselbrockB PorjeszH J EdenbergL J BierutA M Goate
- Resource Type
- Journal article
- Publication Details
- Molecular psychiatry, Vol.14(5), pp.501-510
- DOI
- 10.1038/mp.2008.42
- PMID
- 18414406
- PMCID
- PMC4381434
- ISSN
- 1359-4184
- eISSN
- 1476-5578
- Language
- English
- Electronic publication date
- 04/15/2008
- Date published
- 2009
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics
- Record Identifier
- 9984003961002771
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