title: Predictors of relapse in a bupropion trial for smoking cessation in recently-abstinent alcoholics: preliminary results using an aggregate genetic risk score.
abstract: BACKGROUND
  Rates of smoking in the US population have decreased overall, but rates in some groups, including alcoholic smokers, remain high. Many newly sober alcoholics are concerned about their smoking and some attempt to quit. However, quit rates in this population are low. Prior studies suggest risk for relapse in this population may be genetically influenced and that genetic factors may moderate response to treatment.
  
  
  METHODS
  IN THIS EXPLORATORY STUDY, WE HAD TWO SPECIFIC AIMS: (1) to investigate associations between genetic risk and outcome; (2) to investigate whether genetic risk moderates the efficacy of a medication intervention. Data are from a subsample of 90 participants from a clinical trial of smoking cessation treatment for smokers with between 2 and 12 months of alcohol abstinence. Subjects were randomly assigned to bupropion or placebo. All subjects received counseling and nicotine patches. To examine the possibility that bupropion may have been efficacious in participants with a specific genetic profile (ie, a pharmacogenetic approach), an aggregate genetic risk score was created by combining risk genotypes previously identified in bupropion treatment studies.
  
  
  RESULTS
  Although medication efficacy was not moderated by the aggregate genetic risk score, there was an interaction between nicotine dependence and genetic risk in predicting smoking abstinence rates at the end of treatment (10 weeks).
  
  
  CONCLUSIONS
  Results suggest an aggregate genetic risk score approach may have utility in treatment trials of alcoholics who smoke. Additionally, these findings suggest a strategy for understanding and interpreting conflicting results for single genetic markers examined as moderators of smoking cessation treatment.
authors.affiliation: Providence Veterans Affairs Medical Center, Division of Behavioral Genetics, Rhode Island Hospital and Center for Alcohol and Addiction Studies, Brown University.
authors.forename: John E
authors.initials: JE
authors.lastname: McGeary
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Knopik
authors.forename: John E
authors.initials: JE
authors.lastname: Hayes
authors.forename: Rohan H
authors.initials: RH
authors.lastname: Palmer
authors.forename: Peter M
authors.initials: PM
authors.lastname: Monti
authors.forename: David
authors.initials: D
authors.lastname: Kalman