Journal
BIOLOGICAL PSYCHIATRY
Volume 65, Issue 8, Pages 691-695Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2008.10.004
Keywords
Epidemiology; genetic polymorphism; haplotypes; historical cohort study; smoking cessation
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Funding
- Baden Wurttemberg Ministry of Research, Science and Arts
- German Research Council (DFG) [Br1704/11-1, Da370/5-1, Ru744/4-1, Wi2997/1-1]
- German National Genome Research Project (NGFN)
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Background: Evidence has recently accumulated that single nucleotide polymorphisms in the genetic region encoding the nicotinic acetylcholine receptor subunits alpha-5, alpha-3, and beta-4 are associated with smoking and nicotine dependence. We aimed to determine whether these genetic variations are also predictive of smoking cessation. Methods: Lifetime history of smoking was assessed by questionnaire at enrolment into a large epidemiological study of the German elderly population (ESTHER study). Cox proportional hazards modeling was applied in a retrospective cohort approach to determine the associations of individual polymorphisms and haplotypes with smoking cessation probability in 1446 subjects who reported regularly smoking more than 20 cigarettes at some point in their lives. Results: Given the genotype distributions and number of cessation events observed, the power to detect associations ranged from 54% to 97% for hazard ratios of 1.2 to 1.4 in case of the variant with strongest prior evidence (alpha = .05). Nonetheless, neither individual polymorphisms nor inferred multilocus haplotypes were significantly associated with smoking cessation. Conclusions: Although the robust association of the nicotinic acetylcholine receptor subunit genes investigated with smoking-related phenotypes is an apparent success story of genetic epidemiology, the respective variations seem to exert no relevant influence on smoking cessation probability in heavy smokers in the general population.
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