Document Detail


Variants in the 15q25 gene cluster are associated with risk for schizophrenia and bipolar disorder.
MedLine Citation:
PMID:  23196875     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
CONCLUSION: 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:
Kia J Jackson; Ayman H Fanous; Jingchun Chen; Kenneth S Kendler; Xiangning Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Psychiatric genetics     Volume:  23     ISSN:  1473-5873     ISO Abbreviation:  Psychiatr. Genet.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2012-12-18     Completed Date:  2013-09-20     Revised Date:  2014-06-27    
Medline Journal Info:
Nlm Unique ID:  9106748     Medline TA:  Psychiatr Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  20-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Bipolar Disorder / genetics*
Brain / metabolism,  pathology
Chromosomes, Human, Pair 15 / genetics*
Female
Gene Expression Regulation
Genetic Predisposition to Disease*
Genetic Variation*
Humans
Linkage Disequilibrium / genetics
Male
Middle Aged
Multigene Family / genetics*
Nerve Tissue Proteins / genetics,  metabolism
Receptors, Nicotinic / genetics,  metabolism
Risk Factors
Schizophrenia / genetics*
Grant Support
ID/Acronym/Agency:
1Z01MH002810-01/MH/NIMH NIH HHS; MH-020030/MH/NIMH NIH HHS; MH059556/MH/NIMH NIH HHS; MH074027/MH/NIMH NIH HHS; MH41953/MH/NIMH NIH HHS; N01 MH900001/MH/NIMH NIH HHS; R01 MH041953/MH/NIMH NIH HHS; R01 MH059534/MH/NIMH NIH HHS; R01 MH059548/MH/NIMH NIH HHS; R01 MH59535/MH/NIMH NIH HHS; R01 MH59545/MH/NIMH NIH HHS; R01 MH59565/MH/NIMH NIH HHS; R01 MH59566/MH/NIMH NIH HHS; R01 MH59567/MH/NIMH NIH HHS; R01 MH59571/MH/NIMH NIH HHS; R01 MH59586/MH/NIMH NIH HHS; R01 MH59587/MH/NIMH NIH HHS; R01 MH59588/MH/NIMH NIH HHS; R01 MH60068/MH/NIMH NIH HHS; R01 MH60870/MH/NIMH NIH HHS; R01 MH60879/MH/NIMH NIH HHS; R01 MH67257/MH/NIMH NIH HHS; R01 MH81800/MH/NIMH NIH HHS; U01 MH46276/MH/NIMH NIH HHS; U01 MH46280/MH/NIMH NIH HHS; U01 MH46282/MH/NIMH NIH HHS; U01 MH46289/MH/NIMH NIH HHS; U01 MH46318/MH/NIMH NIH HHS; U01 MH79469/MH/NIMH NIH HHS; U01 MH79470/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/CHRNA5 protein, human; 0/Nerve Tissue Proteins; 0/Receptors, Nicotinic
Comments/Corrections

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