Common variants of IRF3 conferring risk of schizophrenia.

Autor: Li X; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China., Zhang W; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China., Lencz T; The Zucker Hillside Hospital, Psychiatry Research, 75-59 263rd Street, Glen Oaks, NY, USA; Feinstein Institute for Medical Research, 350 Community Drive Manhasset, NY, USA., Darvasi A; Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel., Alkelai A; Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem, Israel., Lerer B; Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem, Israel., Jiang HY; Laboratory for Conservation and Utilization of Bio-resource & Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan University, Kunming, Yunnan, China; Department of Psychiatry, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China., Zhang DF; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China., Yu L; Laboratory for Conservation and Utilization of Bio-resource & Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan University, Kunming, Yunnan, China., Xu XF; Department of Psychiatry, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China., Li M; Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: limingkiz@gmail.com., Yao YG; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China; CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Shanghai, China. Electronic address: yaoyg@mail.kiz.ac.cn.
Jazyk: angličtina
Zdroj: Journal of psychiatric research [J Psychiatr Res] 2015 May; Vol. 64, pp. 67-73. Date of Electronic Publication: 2015 Mar 20.
DOI: 10.1016/j.jpsychires.2015.03.008
Abstrakt: Schizophrenia is a brain disorder with high heritability. Recent studies have implicated genes involved in the immune response pathway in the pathogenesis of schizophrenia. Interferon regulatory factor 3 (IRF3), a virus-immune-related gene, activates the transcription of several interferon-induced genes, and functionally interacts with several schizophrenia susceptibility genes. To test whether IRF3 is a schizophrenia susceptibility gene, we analyzed the associations of its SNPs with schizophrenia in independent population samples as well as reported data from expression quantitative trait loci (eQTL) in healthy individuals. We observed multiple independent SNPs in IRF3 showing nominally significant associations with schizophrenia (P < 0.05); more intriguingly, a SNP (rs11880923), which is significantly correlated with IRF3 expression in independent samples (P < 0.05), is also consistently associated with schizophrenia across different cohorts and in combined samples (odds ratio = 1.075, Pmeta = 2.08 × 10(-5)), especially in Caucasians (odds ratio = 1.078, Pmeta = 2.46 × 10(-5)). These results suggested that IRF3 is likely a risk gene for schizophrenia, at least in Caucasians. Although the clinical associations of IRF3 with diagnosis did not achieve genome-wide level of statistical significance, the observed odds ratio is comparable with other susceptibility loci identified through large-scale genetic association studies on schizophrenia, which could be regarded simply as small but detectable effects.
(Copyright © 2015 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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