Peer smoking and the nicotinic receptor genes: an examination of genetic and environmental risks for nicotine dependence
Article first published online: 15 SEP 2010
© 2010 The Authors, Addiction © 2010 Society for the Study of Addiction
Volume 105, Issue 11, pages 2014–2022, November 2010
How to Cite
Johnson, E. O., Chen, L.-S., Breslau, N., Hatsukami, D., Robbins, T., Saccone, N. L., Grucza, R. A. and Bierut, L. J. (2010), Peer smoking and the nicotinic receptor genes: an examination of genetic and environmental risks for nicotine dependence. Addiction, 105: 2014–2022. doi: 10.1111/j.1360-0443.2010.03074.x
- Issue published online: 6 OCT 2010
- Article first published online: 15 SEP 2010
- Submitted 16 November 2009; initial review completed 15 February 2010; final version accepted 27 April 2010
- Case–control study;
- gene–environmental interaction;
- nicotine dependence;
- nicotinic receptor genes;
- peer smoking
Background Peer smoking provides a socially reinforcing context of friends' encouragement and approval that contributes to smoking behavior. Twin studies show correlations and interactions between peer substance use and genetic liability for substance use. However, none examined specific genes. Here we test the hypothesis that the nicotinic receptor genes CHRNA5 (rs16969968), CHRNA3 (rs578776), CHRNB3 (rs13277254) and CHRND (rs12466358) modify the risk for nicotine dependence associated with peer smoking.
Methods Cases of current nicotine dependence [Fagerström Test for Nicotine Dependence (FTND) ≥ 4] and smoking-exposed (smoked 100+ cigarettes life-time), but non-dependent controls (life-time FTND = 0) came from the Collaborative Genetic Study of Nicotine Dependence (n = 2038). Peer smoking was assessed retrospectively for grades 9–12.
Results Peer smoking and the four single nucleotide polymorphisms (SNPs) were associated with nicotine dependence. A statistically significant interaction was found between peer smoking and rs16969968 (P = 0.0077). Overall risk of nicotine dependence was highest for the rs16969968 AA genotype. However, variance in nicotine dependence attributable to peer smoking was substantially lower among those with the AA genotype at rs16969968 than the lower-risk genotypes: AA = 2.5%, GA/AG = 11.2%, GG = 14.2%; P ≤ 0.004.
Conclusions Peer smoking had a substantially lower effect on nicotine dependence among those with the high-risk AA genotype at the functional SNP rs16969968 (CHRNA5) than among those with lower-risk genotypes. Such results highlight the possibility that given drug exposure those with specific genetic risks may be less affected by social contexts and intervention strategies focused upon social factors could have less influence on those at highest genetic risk.