title: Genetic association of bipolar disorder with the β(3) nicotinic receptor subunit gene.
abstract: OBJECTIVE
  Owing to the clinical relationship between bipolar disorder and nicotine dependence, we investigated two research questions: (i) are genetic associations with nicotine dependence different in individuals with bipolar disorder as compared with individuals without bipolar disorder, and (ii) do loci earlier associated with nicotine dependence have pleiotropic effects on these two diseases.
  
  
  METHODS
  Our study consisted of 916 cases with bipolar disorder and 1028 controls. On the basis of known associations with nicotine dependence, we genotyped eight single-nucleotide polymorphisms (SNPs) on chromosome 8 (three bins) in the regions of CHRNB3 and CHRNA6, and six SNPs on chromosome 15 (three bins) in the regions of CHRNA5 and CHRNA3.
  
  
  RESULTS
  To determine whether the genetic associations with nicotine dependence are different in bipolar disorder than in the general population, we compared allele frequencies of candidate SNPs between individuals with nicotine dependence only and individuals with both nicotine dependence and bipolar disorder. There were no statistical differences between these frequencies, indicating that genetic association with nicotine dependence is similar in individuals with bipolar disorder as in the general population. In the investigation of pleiotropic effects of these SNPs on bipolar disorder, two highly correlated synonymous SNPs in CHRNB3, rs4952 and rs4953, were significantly associated with bipolar disorder (odds ratio 1.7, 95% confidence interval: 1.2-2.4, P=0.001). This association remained significant both after adjusting for a smoking covariate and analyzing the association in nonsmokers only.
  
  
  CONCLUSIONS
  Our results suggest that (i) bipolar disorder does not modify the association between nicotine dependence and nicotinic receptor subunit genes, and (ii) variants in CHRNB3/CHRNA6 are independently associated with bipolar disorder.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Hartz
authors.forename: Peng
authors.initials: P
authors.lastname: Lin
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xuei
authors.forename: Nanette
authors.initials: N
authors.lastname: Rochberg
authors.forename: Scott
authors.initials: S
authors.lastname: Saccone
authors.forename: Wade
authors.initials: W
authors.lastname: Berrettini
authors.forename: Elliot
authors.initials: E
authors.lastname: Nelson
authors.forename: John
authors.initials: J
authors.lastname: Nurnberger
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics
chemical_list: C539371:CHRNB3 protein, human; D021122:Protein Subunits; D011978:Receptors, Nicotinic