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Why do young women smoke? I. Direct and interactive effects of environment, psychological characteristics and nicotinic cholinergic receptor genes

Molecular Psychiatry volume 11, pages 312–322 (2006)Cite this article

Abstract

Despite the health hazards, cigarette smoking is disproportionately frequent among young women. A significant contribution of genetic factors to smoking phenotypes is well established. Efforts to identify susceptibility genes do not generally take into account possible interaction with environment, life experience and psychological characteristics. We recruited 501 female Israeli students aged 20–30 years, obtained comprehensive background data and details of cigarette smoking and administered a battery of psychological instruments. Smoking initiators (n=242) were divided into subgroups with high (n=127) and low (n=115) levels of nicotine dependence based on their scores on the Fagerstrom Tolerance Questionnaire and genotyped with noninitiators (n=142) for single nucleotide polymorphisms (SNPs) in 11 nicotinic cholinergic receptor genes. We found nominally significant (P<0.05) allelic and genotypic association with smoking initiation of SNP rs2072660 and multilocus haplotypes (P<0.007–0.05) in CHRNB2 and nominal (P<0.05) allelic or genotypic association of SNPs in CHRNA7 (rs1909884), CHRNA9 (rs4861065) and CHRNB3 (rs9298629) with nicotine dependence. Employing logistic regression and controlling for known risk factors, the best-fitting model for smoking initiation encompassed a 5 SNP haplotype in CHRNB2, neuroticism and novelty seeking (P=5.9 × 10−14, Nagelkerke r2=0.30). For severity of nicotine dependence, two SNPs in CHRNA7 (rs1909884 and rs883473), one SNP in CHRNA5 (rs680244) and the interaction of a SNP in CHRNA7 (rs2337980) with neuroticism, were included in the model (P=2.24 × 10−7, Nagelkerke r2=0.40). These findings indicate that background factors, psychological characteristics and genetic variation in nicotinic cholinergic receptors contribute independently or interactively to smoking initiation and to severity of nicotine dependence in young women.

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Acknowledgements

Research described in this article was supported in part by Philip Morris USA Inc. and Philip Morris International (investigator designed, independently reviewed grant), the Genome Infrastructure Program of the Israeli Ministry of Science and Technology and the Crown Human Genome Center at the Weizmann Institute of Science. The authors thank Naomi Boumard and Professor Benny Yakir for their helpful advice.

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  1. L Greenbaum and K Kanyas: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    L Greenbaum, K Kanyas, O Karni & B Lerer

  2. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel

    Y Merbl, T Olender, A Horowitz, A Yakir, D Lancet & E Ben-Asher

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  1. L Greenbaum
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Greenbaum, L., Kanyas, K., Karni, O. et al. Why do young women smoke? I. Direct and interactive effects of environment, psychological characteristics and nicotinic cholinergic receptor genes. Mol Psychiatry 11, 312–322 (2006). https://doi.org/10.1038/sj.mp.4001774

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