title: Variants near CHRNB3-CHRNA6 are associated with DSM-5 cocaine use disorder: evidence for pleiotropy.
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.
authors.affiliation: 1] School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, USA [2] Department of Psychiatry, Washington University, St. Louis, MO, USA.
authors.forename: Brooke
authors.initials: B
authors.lastname: Sadler
authors.affiliation: 1] Department of Psychiatry, Washington University, St. Louis, MO, USA [2] Department of Genetics, Washington University, St. Louis, MO, USA.
authors.forename: Gabe
authors.initials: G
authors.lastname: Haller
authors.affiliation: Department of Psychiatry, Washington University, St. Louis, MO, USA.
authors.forename: Arpana
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Rob
authors.initials: R
authors.lastname: Culverhouse
authors.affiliation: Department of Psychiatry, Washington University, St. Louis, MO, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Bucholz
authors.affiliation: Department of Genetics, Rutgers University, Piscataway, NJ.
authors.forename: Andy
authors.initials: A
authors.lastname: Brooks
authors.affiliation: Department of Genetics, Rutgers University, Piscataway, NJ.
authors.forename: Jay
authors.initials: J
authors.lastname: Tischfield
authors.affiliation: Division of Health, Social and Economic Research, Research Triangle Institute International, Research Triangle Park, NC.
authors.forename: Eric O
authors.initials: EO
authors.lastname: Johnson
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Howard
authors.initials: H
authors.lastname: Edenberg
authors.affiliation: Department of Psychiatry, University of California-San Diego, La Jolla, CA.
authors.forename: Marc
authors.initials: M
authors.lastname: Schuckit
authors.affiliation: Department of Genetics, Washington University, St. Louis, MO, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Saccone
authors.affiliation: Department of Psychiatry, Washington University, St. Louis, MO, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Bierut
authors.affiliation: 1] Department of Psychiatry, Washington University, St. Louis, MO, USA [2] Department of Genetics, Washington University, St. Louis, MO, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
mesh_terms: D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics; D019970:Cocaine-Related Disorders / Q000175:diagnosis* / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics
chemical_list: C470410:CHRNA6 protein, human; C539371:CHRNB3 protein, human; D011978:Receptors, Nicotinic