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Sci Rep. 2014 Mar 28;4:4497. doi: 10.1038/srep04497.

Variants near CHRNB3-CHRNA6 are associated with DSM-5 cocaine use disorder: evidence for pleiotropy.

Author information

1
1] School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, USA [2] Department of Psychiatry, Washington University, St. Louis, MO, USA.
2
1] Department of Psychiatry, Washington University, St. Louis, MO, USA [2] Department of Genetics, Washington University, St. Louis, MO, USA.
3
Department of Psychiatry, Washington University, St. Louis, MO, USA.
4
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
5
Department of Genetics, Rutgers University, Piscataway, NJ.
6
Division of Health, Social and Economic Research, Research Triangle Institute International, Research Triangle Park, NC.
7
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN.
8
Department of Psychiatry, University of California-San Diego, La Jolla, CA.
9
Department of Genetics, Washington University, St. Louis, MO, USA.

Abstract

In the U.S.A., cocaine is the second most abused illicit drug. Variants within the CHRNB3-A6 gene cluster have been associated with cigarette consumption in several GWAS. These receptors represent intriguing candidates for the study of cocaine dependence because nicotinic receptors are thought to be involved in generalized addiction pathways. Using genotypic data from a GWAS of the Study of Addiction: Genetics and Environment (SAGE) dataset, we tested for association of CHRNB3-A6 SNPs with DSM-5 cocaine use disorder. Multiple SNPs in the region were significantly associated with increased risk of cocaine use disorder. Inclusion of the most significant SNP as a covariate in a linear regression model provided evidence for an additional independent signal within this locus for cocaine use disorder. These results suggest that the CHRNB3-A6 locus contains multiple variants affecting risk for vulnerability to cocaine and nicotine dependence as well as bipolar disorder, suggesting that they have pleiotropic effects.

PMID:
24675634
PMCID:
PMC4894386
DOI:
10.1038/srep04497
[Indexed for MEDLINE]
Free PMC Article

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