title: CHRNA5/A3/B4 Variant rs3743078 and Nicotine-Related Phenotypes: Indirect Effects Through Nicotine Craving.
abstract: OBJECTIVE
  Nicotine craving is considered an important element in the persistence of cigarette smoking, but little is known about the role of craving in the widely recognized association between variants mapped to the neuronal nicotinic acetylcholine receptor (CHRN) genes on chromosome 15 and nicotine phenotypes.
  
  
  METHODS
  The associations between CHRNA5-CHRNA3-CHRNB4 variants and cigarettes per day (CPD), the Fagerström Test for Nicotine Dependence (FTND), and craving were analyzed in data from 662 lifetime smokers from an Israeli adult Jewish household sample. Indirect effects of genotype on nicotine phenotypes through craving were formally tested using regression and bootstrapping procedures.
  
  
  RESULTS
  At CHRNA3, allele G of rs3743078 was associated with increased craving, CPD, and FTND scores: Participants with one or two copies of the G allele had, on average, higher scores on the craving scale (p = .0025), more cigarettes smoked (p = .0057), and higher scores on the FTND (p =.0024). With craving in the model, variant rs3743078 showed a significant indirect effect through craving on CPD (p = .0026) and on FTND score (p = .0024). A sizeable proportion of the total rs3743078 effect on CPD (56.4%) and FTND (65.2%) was indirect through craving.
  
  
  CONCLUSIONS
  These results suggest that nicotine craving may play a central role in nicotine use disorders and may have utility as a therapeutic target.
authors.affiliation: Department of Psychiatry, Columbia University, NewYork, NewYork.|NewYork State Psychiatric Institute, NewYork, NewYork.
authors.forename: Dvora
authors.initials: D
authors.lastname: Shmulewitz
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, NewYork, NewYork.
authors.forename: Jacquelyn L
authors.initials: JL
authors.lastname: Meyers
authors.affiliation: Department of Psychiatry, Columbia University, NewYork, NewYork.|NewYork State Psychiatric Institute, NewYork, NewYork.|Department of Biostatistics, Mailman School of Public Health, Columbia University, NewYork, NewYork.
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Wall
authors.affiliation: Department of Psychiatry, Columbia University, NewYork, NewYork.|NewYork State Psychiatric Institute, NewYork, NewYork.
authors.forename: Efrat
authors.initials: E
authors.lastname: Aharonovich
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Felsenstein Medical Research Center, Petach Tikva, Israel.
authors.forename: Amos
authors.initials: A
authors.lastname: Frisch
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Baruch
authors.initials: B
authors.lastname: Spivak
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Felsenstein Medical Research Center, Petach Tikva, Israel.|Research Unit, Geha Mental Health Center, Petach Tikva, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
authors.affiliation: Departments of Biochemistry and Molecular Biology and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.affiliation: Departments of Psychiatry and Genetics and Neurobiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.affiliation: Department of Psychiatry, Columbia University, NewYork, NewYork.|NewYork State Psychiatric Institute, NewYork, NewYork.|Department of Epidemiology, Mailman School of Public Health, Columbia University, NewYork, NewYork.
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Hasin
mesh_terms: D000328:Adult; D066249:Craving / Q000502:physiology*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000175:diagnosis / Q000235:genetics; D055815:Young Adult
chemical_list: D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human; C447159:CHRNB4 protein, human