title: Are genetic variants for tobacco smoking associated with cannabis involvement?
abstract: BACKGROUND
  Cannabis users are highly likely to also be tobacco cigarette smokers and a proportion of this comorbidity is attributable to shared genetic influences. Three large meta-analyses of genomewide association studies (GWAS) of tobacco smoking have identified multiple genomewide significant (p<5×10(-8)) single nucleotide polymorphisms (SNPs). We examine whether these SNPs are associated with tobacco smoking and with cannabis involvement in an independent sample.
  
  
  METHODS
  Eleven SNPs associated with cigarettes per day (CPD), ever versus never smoking and current smoking/smoking cessation at p<5×10(-8) were selected from three published meta-analyses. Association analyses were conducted with similar tobacco smoking measures in 2716 European-American subjects from the Study of Addictions Genes and Environment (SAGE) and with lifetime and current cannabis use and DSM-IV cannabis abuse/dependence.
  
  
  RESULTS
  Cannabis use and tobacco smoking correlated at 0.54. Rs16969968 in CHRNA5 (and its proxy, rs1051730 in CHRNA3) and rs1451240, a proxy for rs13280604 in CHRNB3, were associated with CPD after Bonferroni correction (p<0.006). rs1451240 was also associated with DSM-IV cannabis abuse/dependence. Rs6265 in BDNF was associated with smoking initiation, as in the original meta-analysis and also with lifetime cannabis use. Associations with cannabis involvement were no longer significant upon adjustment for the tobacco smoking measures.
  
  
  CONCLUSIONS
  The modest associations between cannabis involvement and SNPs for tobacco smoking were not independent of the comorbidity between tobacco and cannabis involvement. Larger samples of individuals might be required to articulate the specific genetic architecture of cannabis involvement.
authors.affiliation: Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA. Electronic address: arpana@wustl.edu.
authors.forename: Arpana
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Institute of Psychiatry, Addictions Department, London, UK.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lynskey
authors.affiliation: Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
authors.forename: Manav
authors.initials: M
authors.lastname: Kapoor
authors.affiliation: Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Bucholz
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.affiliation: University of California, San Diego, CA, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Schuckit
authors.affiliation: Rutgers University, Department of Genetics, Piscataway, NJ, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Brooks
authors.affiliation: University of Connecticut Health Center, Department of Psychiatry, Farmington, CT, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Hesselbrock
authors.affiliation: University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kramer
authors.affiliation: Washington University School of Medicine, Department of Genetics, St. Louis, MO, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Saccone
authors.affiliation: University of California, San Diego, CA, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Tischfield
authors.affiliation: Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016739:Behavior, Addictive / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics; D012907:Smoking / Q000235:genetics*; D016540:Smoking Cessation; D055815:Young Adult
chemical_list: D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human
keywords: Cannabis; Chrna5; Tobacco