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Human Molecular Genetics Advance Access originally published online on November 30, 2007
Human Molecular Genetics 2008 17(5):724-734; doi:10.1093/hmg/ddm344
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The neuronal nicotinic receptor subunit genes (CHRNA6 and CHRNB3) are associated with subjective responses to tobacco

Joanna S. Zeiger1,{dagger}, Brett C. Haberstick1,4,{dagger}, Isabel Schlaepfer1,2, Allan C. Collins1,3, Robin P. Corley1, Thomas J. Crowley4, John K. Hewitt1,3, Christian J. Hopfer4, Jeffrey Lessem1, Matthew B. McQueen1,3, Soo Hyun Rhee1,3 and Marissa A. Ehringer1,2,*

1 Institute for Behavioral Genetics 2 Department of Integrative Physiology and 3 Department of Psychology, University of Colorado, Boulder, CO, USA and 4 Division of Substance Dependence, Department of Psychiatry, University of Colorado School of Medicine, Denver, CO, USA

* To whom correspondence should be addressed at: Institute for Behavioral Genetics 447 UCB, University of Colorado, Boulder, CO 80309, USA. Tel: +1 303 492 1464; Fax: +1 303 492 8063; Email: marissa.ehringer{at}colorado.edu

Received October 9, 2007; Accepted November 22, 2007

Neuronal nicotinic acetylcholine receptors have been implicated in various measures of nicotine dependence. In this paper, we present findings from an exploratory study of single nucleotide polymorphisms (SNPs) in the CHRNB3 and CHRNA6 genes with tobacco and alcohol phenotypes, including frequency of use and three subjective response factors occurring shortly after initiation of use. Subjects were 1056 ethnically diverse adolescents ascertained from clinical and community settings. The most significant associations were found between two CHRNB3 SNPs (rs4950 and rs13280604) and the three subjective response factors to initial tobacco use. These findings were replicated in a separate community sample of 1524 families participating in the National Longitudinal Study of Adolescent Health. Both CHRNB3 SNPs were found to be associated with similar measures of subjective response to tobacco. These results indicate that early subjective response to nicotine may be a valuable endophenotype for genetic studies aimed at uncovering genes contributing to nicotine use and addiction.

{dagger} The authors wish it to be known that, in their opinion, the first 2 authors should be regarded as joint First Authors.


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