Institutional members access full text with Ovid®

Share this article on:

Variants in the 15q25 gene cluster are associated with risk for schizophrenia and bipolar disorder

Jackson, Kia J.a; Fanous, Ayman H.a,b,c; Chen, Jingchuna; Kendler, Kenneth S.a; Chen, Xiangninga

doi: 10.1097/YPG.0b013e32835bd5f1
Original Articles

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.

Supplemental Digital Content is available in the text.

aDepartment of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia

bWashington VA Medical Center

cGeorgetown University Medical Center, Washington, District of Columbia, USA

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.psychgenetics.com).

Correspondence to Xiangning Chen, PhD, Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, 800 E. Leigh St., Suite 390A, Richmond, VA 23219, USA Tel: +1 804 828 8124; fax: +1 804 828 1471; e-mail: xchen@vcu.edu

Received May 16, 2012

Accepted September 1, 2012

© 2013 Lippincott Williams & Wilkins, Inc.