Interplay of genetic risk (CHRNA5) and environmental risk (partner smoking) on cigarette smoking reduction - PubMed (original) (raw)

Observational Study

Interplay of genetic risk (CHRNA5) and environmental risk (partner smoking) on cigarette smoking reduction

Li-Shiun Chen et al. Drug Alcohol Depend. 2014.

Abstract

Background: This study tests whether the genetic predictor (CHRNA5 nicotine receptor gene variants) and an environmental risk factor (partner smoking) interact in the prediction of smoking reduction.

Methods: Subjects were from a community-based, longitudinal study of women (n=1856) who smoked before pregnancy, and a randomized comparative effectiveness smoking cessation trial (n=1065). Smoking reduction was defined as the trajectory of self-reported smoking quantities over time in the observational study, and as the trajectory of alveolar CO levels in the cessation trial.

Results: In the pregnancy study, rs16969968 genotype and partner smoking status interacted such that the smoking reduction was lowest for expectant mothers with high genetic risk and partner smoking, and highest for those with high genetic risk but not partner smoking (interaction of genotype×partner smoking on smoking quantity trajectory slope β=0.071, 95%CI=0.013, 0.13, p=0.017). In the clinical trial, a similar interaction was found (interaction β=0.20, 95%CI=0.049, 0.36, p=0.010). Furthermore, these associations were moderated by pharmacotherapy such that the interactive relation of genetic and environmental factors occurred in the placebo group, but not in the active pharmacotherapy group (interaction of genotype×partner smoking×pharmacotherapy on CO trajectory slope β=-0.25, 95%CI=-0.42, -0.091, p=0.0023).

Conclusions: The CHRNA5 genetic risk synergized the effect of partner smoking, producing an especially low likelihood of successful smoking reduction in two complementary studies. This suggests that the genetic vulnerability may be mitigated by altering environmental factors. In addition, cessation pharmacotherapy neutralizes the increase in cessation failure associated with combined genetic and environmental risks, which has possible relevance to treatment algorithms.

Keywords: ALSPAC; CHRNA5; Partner smoking; Smoking reduction; UW-TTURC.

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Conflict of interest statement

Conflict of Interest: Laura J. Bierut is listed as an inventor on issued U.S. Patent 8,080,371, “Markers for Addiction” covering the use of certain SNPs in determining the diagnosis, prognosis, and treatment of addiction. All other authors declare no potential conflict of interest.

Figures

Figure 1

Convergent results in two independent samples: Environmental effect (partner smoking) on quitting is stronger in individuals with CHRNA5 risk allele: Convergent results in two independent samples of un-medicated smokers (A) and (B) Interaction of rs16969968 and partner smoking on quitting (decrease of smoking quantity over time) is significant. (b=0.071, 95% CI 0.013-0.13, p=0.017 in ALSPAC, and b=0.20, 95%CI 0.049-0.36, p=0.010 in TTURC). (B) and (C) Medication neutralizes the G effect (b=-0.092, 95% CI=-0.17 to -0.016, 0.018). Medication neutralizes the G*E effect (b=-0.25, 95% CI=-0.42 to -0.091, p=0.0023) Reported data points indicate means in each group for that time points. *CPD coding for 4 levels (0-1, 1=1-9, 2=10-19, 3=20 or more).

Figure 2

Medication effect on post-quit smoking quantity is moderated by both CHRNA5 rs16969968 genotypes and partner smoking status [Table: see text]

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Interplay of genetic risk (CHRNA5) and environmental risk (partner smoking) on cigarette smoking reduction - PubMed (original) (raw)