title: Dissection of the phenotypic and genotypic associations with nicotinic dependence.
abstract: BACKGROUND
  Strong evidence demonstrates that nicotine dependence is associated with 4 genetic variants rs16969968, rs6474412, rs3733829, and rs1329650 in large-scale Genome-Wide Association Studies. We examined how these identified genetic variants relate to nicotine dependence defined by different categorical and dimensional measures.
  
  
  METHODS
  Four genetic variants were analyzed in 2,047 subjects of European descent (1,062 cases and 985 controls). Nicotine dependence was assessed with multiple smoking measures, including the Fagerström Test for Nicotine Dependence, the Diagnostic and Statistical Manual for Mental Disorders-IV (DSM-IV) nicotine dependence, the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking Dependence Motives. Single-item measures of cigarettes per day (CPD) and time to first cigarette (TTF) in the morning were also examined.
  
  
  RESULTS
  Among the variants, association effect sizes were largest for rs16969968, with measures of craving and heavy smoking, especially cigarettes smoked per day, showing the largest effects. Significant but weaker associations were found for rs6474412 and rs3733729 but not for rs1329650. None of the more comprehensive measures of smoking behaviors yielded stronger genetic associations with these variants than did CPD.
  
  
  CONCLUSIONS
  CPD is an important simple measure that captures in part the genetic associations of CHRNA5 and nicotine dependence, even when other more comprehensive measures of smoking behaviors are examined. The CHRNA5 gene is associated with heavy compulsive smoking and craving; this should inform the mission to improve the diagnostic validity of DSM-V.
authors.affiliation: Department of Psychiatry (Box 8134), Washington University School of Medicine, 660S. Euclid Ave., St. Louis, MO 63110, USA. chenli@psychiatry.wustl.edu
authors.forename: Li-Shiun
authors.initials: LS
authors.lastname: Chen
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Baker
authors.forename: Richard
authors.initials: R
authors.lastname: Grucza
authors.forename: Jen C
authors.initials: JC
authors.lastname: Wang
authors.forename: Eric O
authors.initials: EO
authors.lastname: Johnson
authors.forename: Naomi
authors.initials: N
authors.lastname: Breslau
authors.forename: Dorothy
authors.initials: D
authors.lastname: Hatsukami
authors.forename: Stevens S
authors.initials: SS
authors.lastname: Smith
authors.forename: Nancy
authors.initials: N
authors.lastname: Saccone
authors.forename: Scott
authors.initials: S
authors.lastname: Saccone
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
authors.forename: Alison M
authors.initials: AM
authors.lastname: Goate
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic
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