Variants near CHRNB3-CHRNA6 are associated with DSM-5 cocaine use disorder

Evidence for pleiotropy

Brooke Sadler, Gabe Haller, Arpana Agrawal, Rob Culverhouse, Kathleen Bucholz, Andy Brooks, Jay Tischfield, Eric O. Johnson, Howard Edenberg, Marc Schuckit, Nancy Saccone, Laura Bierut, Alison Goate

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number4497
JournalScientific Reports
Volume4
DOIs
StatePublished - Mar 28 2014

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Cocaine
Single Nucleotide Polymorphism
Cocaine-Related Disorders
Genome-Wide Association Study
Linear Models
Tobacco Use Disorder
Nicotinic Receptors
Street Drugs
Multigene Family
Bipolar Disorder
Tobacco Products

ASJC Scopus subject areas

  • General

Cite this

Sadler, B., Haller, G., Agrawal, A., Culverhouse, R., Bucholz, K., Brooks, A., ... Goate, A. (2014). Variants near CHRNB3-CHRNA6 are associated with DSM-5 cocaine use disorder: Evidence for pleiotropy. Scientific Reports, 4, [4497]. https://doi.org/10.1038/srep04497

Variants near CHRNB3-CHRNA6 are associated with DSM-5 cocaine use disorder : Evidence for pleiotropy. / Sadler, Brooke; Haller, Gabe; Agrawal, Arpana; Culverhouse, Rob; Bucholz, Kathleen; Brooks, Andy; Tischfield, Jay; Johnson, Eric O.; Edenberg, Howard; Schuckit, Marc; Saccone, Nancy; Bierut, Laura; Goate, Alison.

In: Scientific Reports, Vol. 4, 4497, 28.03.2014.

Research output: Contribution to journalArticle

Sadler, B, Haller, G, Agrawal, A, Culverhouse, R, Bucholz, K, Brooks, A, Tischfield, J, Johnson, EO, Edenberg, H, Schuckit, M, Saccone, N, Bierut, L & Goate, A 2014, 'Variants near CHRNB3-CHRNA6 are associated with DSM-5 cocaine use disorder: Evidence for pleiotropy', Scientific Reports, vol. 4, 4497. https://doi.org/10.1038/srep04497
Sadler, Brooke ; Haller, Gabe ; Agrawal, Arpana ; Culverhouse, Rob ; Bucholz, Kathleen ; Brooks, Andy ; Tischfield, Jay ; Johnson, Eric O. ; Edenberg, Howard ; Schuckit, Marc ; Saccone, Nancy ; Bierut, Laura ; Goate, Alison. / Variants near CHRNB3-CHRNA6 are associated with DSM-5 cocaine use disorder : Evidence for pleiotropy. In: Scientific Reports. 2014 ; Vol. 4.
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