title: Variants in the 15q25 gene cluster are associated with risk for schizophrenia and bipolar disorder.
abstract: BACKGROUND
  Rates of tobacco smoking are significantly higher in patients with schizophrenia compared with the general population. The underlying mechanism for this comorbidity is unclear. One hypothesis is that there are common genetic factors that predispose to both nicotine dependence (ND) and schizophrenia. To investigate this hypothesis, we examined the association of the 15q25 gene cluster, the most significant candidate region to date implicated in ND and smoking behavior, with schizophrenia and bipolar disorder.
  
  
  METHODS
  Five variants in the 15q25 gene cluster (rs951266, rs16969968, rs1051730, rs8040868, and rs17477223) were selected to test for association with schizophrenia diagnosis, bipolar disorder diagnosis, and the presence of negative symptoms of schizophrenia. Effects of the variants on 15q25 gene expression were analyzed using publically available postmortem brain expression data.
  
  
  RESULTS
  A meta-analysis revealed four markers associated with risk for schizophrenia and bipolar disorder (rs951266, rs16969968, rs8040868, and rs17477223), and with the presence of negative symptoms of schizophrenia (rs951266, rs1051730, rs8040868, and rs17477223). The associations were in the same direction as that found for ND. Gene expression analysis indicated an association between genotypes of the rs1051730 variant and CHRNA5 expression in brain and peripheral blood mononuclear cells, and with the rs16969968 and rs17477223 variants in brain.
  
  
  CONCLUSIONS
  Variants in the 15q25 gene cluster are associated with risk for schizophrenia/bipolar illness, negative symptoms of schizophrenia, and influence CHRNA5 expression in the brain and peripheral blood mononuclear cells. These results are consistent with the notion that there are genetic mechanisms common to schizophrenia, ND, and bipolar disorder.
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia 23219, USA.
authors.forename: Kia J
authors.initials: KJ
authors.lastname: Jackson
authors.forename: Ayman H
authors.initials: AH
authors.lastname: Fanous
authors.forename: Jingchun
authors.initials: J
authors.lastname: Chen
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.forename: Xiangning
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic