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. 2009 Feb;34(3):698-706.
doi: 10.1038/npp.2008.122. Epub 2008 Aug 13.

Genetic association of the CHRNA6 and CHRNB3 genes with tobacco dependence in a nationally representative sample

Nicole R Hoft  1 , Robin P Corley, Matthew B McQueen, Isabel R Schlaepfer, David Huizinga, Marissa A Ehringer
Affiliations

Genetic association of the CHRNA6 and CHRNB3 genes with tobacco dependence in a nationally representative sample

Nicole R Hoft et al. Neuropsychopharmacology. 2009 Feb.

Abstract

Neuronal nicotinic acetylcholine receptors are activated by both endogenous acetylcholine and exogenous nicotine, making sequence variations in these receptors likely candidates for association with tobacco phenotypes. Previous studies have found evidence for significant association between single nucleotide polymorphisms (SNPs) in the genomic region containing the CHRNA6 and CHRNB3 genes and tobacco behaviors. In this study, we provide support for an association between these genes and tobacco dependence in the National Youth Survey Family Study wave 10, a nationally representative sample of households. Eight SNPs in the CHRNA6 and CHRNB3 genomic region were genotyped in 1051 subjects, approximately half of whom are members of sibling pairs. Genetic association with DSM-IV dependence was assessed using a family-based approach as implemented in the statistical package PBAT. Individual SNPs were tested for association with quit attempts and overall dependence. Variation in CHRNA6 was found to be associated with tobacco dependence (p=0.007 in Caucasians). SNPs in CHRNB3 were found to be associated with the number of quit attempts (p=0.0024). Together these results further implicate the region downstream of CHRNA6 and the region upstream of CHRNB3 in risk of nicotine dependence.

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Conflict of interest statement

Disclosures and Potential Conflicts of Interest

Dr. Nicole R. Hoft, Isabel R. Schlaepfer, Dr. Robin P. Corley, Dr. Matthew B. McQueen, Dr. David Huizinga, and Dr. Marissa A. Ehringer do not have any potential conflicts of interest, financial or otherwise, relevant to the subject matter of this work.

Figures

Figure 1
Figure 1
Cartoon representation of the CHRNA6-CHRNB3 locus. Boxes represent exons separated by intronic regions (not drawn to scale). Eight SNPs were genotyped shown in bold, with their reference sequence numbers and gene locations indicated. The number of nucleotide base pairs (bp) between each SNP, and the linkage disequilibrium measured by r2, is also indicated.
Figure 2
Figure 2
Association results for number of quit attempts (a) and nicotine dependence (b) and across the CHRNA6 CHRNB3 region. The y-axis shows p-values for each SNP across the x-axis for each of the three different sample subsets.
Figure 2
Figure 2
Association results for number of quit attempts (a) and nicotine dependence (b) and across the CHRNA6 CHRNB3 region. The y-axis shows p-values for each SNP across the x-axis for each of the three different sample subsets.
See this image and copyright information in PMC

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