title: Multiple distinct CHRNB3-CHRNA6 variants are genetic risk factors for nicotine dependence in African Americans and European Americans.
abstract: OBJECTIVE
  Studies have shown association between common variants in the α6-β3 nicotinic receptor subunit gene cluster and nicotine dependence in European ancestry populations. We investigate whether this generalizes to African Americans, whether the association is specific to nicotine dependence and whether this region contains additional genetic contributors to nicotine dependence.
  
  
  METHODS
  We examined consistency of association across studies and race between the α6β3 nicotinic receptor subunit locus and nicotine, alcohol, marijuana and cocaine dependence in three independent studies.
  
  
  METHODS
  United States of America.
  
  
  METHODS
  European Americans and African Americans from three case-control studies of substance dependence.
  
  
  METHODS
  Subjects were evaluated using the Semi-Structured Assessment for the Genetics of Alcoholism. Nicotine dependence was determined using the Fagerström Test for Nicotine Dependence.
  
  
  RESULTS
  The single nucleotide polymorphism rs13273442 was associated significantly with nicotine dependence across all three studies in both ancestry groups [odds ratio (OR) = 0.75, P = 5.8 × 10(-4) European Americans; OR = 0.80, P = 0.05 African Americans]. No other substance dependence was associated consistently with this variant in either group. Another SNP in the region, rs4952, remains modestly associated with nicotine dependence in the combined data after conditioning on rs13273442.
  
  
  CONCLUSIONS
  The common variant rs13273442 in the CHRNB3-CHNRA6 region is associated significantly with nicotine dependence in European Americans and African Americans across studies recruited for nicotine, alcohol and cocaine dependence. Although these data are modestly powered for other substances, our results provide no evidence that correlates of rs13273442 represent a general substance dependence liability. Additional variants probably account for some of the association of this region to nicotine dependence.
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA; Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Culverhouse
authors.forename: Eric O
authors.initials: EO
authors.lastname: Johnson
authors.forename: Naomi
authors.initials: N
authors.lastname: Breslau
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Hatsukami
authors.forename: Brooke
authors.initials: B
authors.lastname: Sadler
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Brooks
authors.forename: Victor M
authors.initials: VM
authors.lastname: Hesselbrock
authors.forename: Marc A
authors.initials: MA
authors.lastname: Schuckit
authors.forename: Jay A
authors.initials: JA
authors.lastname: Tischfield
authors.forename: Alison M
authors.initials: AM
authors.lastname: Goate
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Saccone
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: C470410:CHRNA6 protein, human; C539371:CHRNB3 protein, human; D011978:Receptors, Nicotinic
keywords: African Americans; European Americans; chromosome 8; genetic risk; rs13273442; rs1451240; rs4952; rs6474412; substance dependence