Declaration of interest: none.
Article first published online: 5 JAN 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 159B, Issue 2, pages 227–235, March 2012
How to Cite
Bousman, C. A., Rivard, C., Haese, J. D., Ambrosone, C. and Hyland, A. (2012), Alpha-5 and -3 nicotinic receptor gene variants predict nicotine dependence but not cessation: Findings from the COMMIT cohort. Am. J. Med. Genet., 159B: 227–235. doi: 10.1002/ajmg.b.32019
How to Cite this Article: Bousman CA, Rivard C, Haese JD, Ambrosone C, Hyland A. 2012. Alpha-5 and -3 Nicotinic Receptor Gene Variants Predict Nicotine Dependence But Not Cessation: Findings From the COMMIT Cohort. Am J Med Genet Part B 159B:227–235.
- Issue published online: 12 JAN 2012
- Article first published online: 5 JAN 2012
- Manuscript Accepted: 9 DEC 2011
- Manuscript Received: 18 SEP 2011
- NCI. Grant Number: 5R01CA100802
Smoking many cigarettes per day (CPD) and short interval to first cigarette (TTF) after waking are two of the most heritable smoking phenotypes and comprise the Heavy Smoking Index (HSI). These phenotypes are often used as proxies for nicotine dependence (ND) and are associated with smoking cessation outcomes. Case–control and genome-wide association studies have reported links between single nucleotide polymorphisms (SNPs) in the alpha-5 and -3 nicotinic receptor subunit (CHRNA5 and CHRNA3) genes and CPD but few have examined TTF or cessation outcomes. In this study we longitudinally assessed 1301 European-American smokers at four time-points from 1988 to 2005. One CHRNA5 (rs16969968) and two CHRNA3 (rs1051703, rs6495308) SNPs were examined for their ability to predict smokers who “ever” reported ND based on three phenotypic classifications: (1) 25+ CPD, (2) TTF < 10 min, and (3) HSI ≥ 4. In a subsample of 1157 quit attempters, we also examined each SNP's ability to predict “ever” quitting for a period of >6 months. Demographically adjusted logistic regressions showed significant allelic and genotypic associations between all three SNPs and CPD but not TTF, HSI, or smoking cessation. Carriers of both the rs16969968-AA and rs6495308-TT genotypes had approximately twofold greater odds for ND defined using CPD or TTF. Results suggest nicotinic receptor variants are associated with greater odds of ND according to CPD and to a lesser extent TTF. Research examining the effect of nicotinic receptor genetic variation on ND phenotypes beyond CPD is warranted. © 2012 Wiley Periodicals, Inc.