title: Interplay of genetic risk (CHRNA5) and environmental risk (partner smoking) on cigarette smoking reduction.
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.
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, United States. Electronic address: chenli@psychiatry.wustl.edu.
authors: Li-Shiun
authors: LS
authors: Chen
authors: Tobacco Research and Intervention, University of Wisconsin, School of Medicine, Madison, WI 53711, United States.
authors: Timothy B
authors: TB
authors: Baker
authors: Tobacco Research and Intervention, University of Wisconsin, School of Medicine, Madison, WI 53711, United States.
authors: Megan E
authors: ME
authors: Piper
authors: Tobacco Research and Intervention, University of Wisconsin, School of Medicine, Madison, WI 53711, United States.
authors: Stevens S
authors: SS
authors: Smith
authors: Division of Biostatistics, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors: Charles
authors: C
authors: Gu
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors: Richard A
authors: RA
authors: Grucza
authors: Avon Longitudinal Study of Parents and Children (ALSPAC), School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
authors: George Davey
authors: GD
authors: Smith
authors: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, United Kingdom.
authors: Marcus
authors: M
authors: Munafo
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors: Laura J
authors: LJ
authors: Bierut
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D011247:Pregnancy; D055815:Young Adult; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D008137:Longitudinal Studies; D009419:Nerve Tissue Proteins / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000523:psychology; D016540:Smoking Cessation / Q000523:psychology; D018454:Spouses / Q000523:psychology; D061485:Tobacco Use Cessation Devices; D014029:Tobacco Use Disorder / Q000235:genetics / Q000523:psychology; D044465:White People / Q000235:genetics / Q000523:psychology
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic
keywords: ALSPAC; CHRNA5; Partner smoking; Smoking reduction; UW-TTURC