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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Bipolar Disorder / genetics
  • Cocaine-Related Disorders / diagnosis*
  • Cocaine-Related Disorders / genetics*
  • Gene Frequency
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Receptors, Nicotinic / genetics*
  • Tobacco Use Disorder / genetics


  • CHRNA6 protein, human
  • CHRNB3 protein, human
  • Receptors, Nicotinic