학술논문

Variants near CHRNB3-CHRNA6 are associated with DSM-5 cocaine use disorder: evidence for pleiotropy.
Document Type
article
Source
Subject
Alleles
Bipolar Disorder
Cocaine-Related Disorders
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Variation
Haplotypes
Humans
Linkage Disequilibrium
Odds Ratio
Polymorphism
Single Nucleotide
Receptors
Nicotinic
Tobacco Use Disorder
Language
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.