title: Common variants of IRF3 conferring risk of schizophrenia.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Todd
authors.initials: T
authors.lastname: Lencz
authors.affiliation: Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Darvasi
authors.affiliation: Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Alkelai
authors.affiliation: Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lerer
authors.affiliation: 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.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Deng-feng
authors.initials: DF
authors.lastname: Zhang
authors.affiliation: Laboratory for Conservation and Utilization of Bio-resource & Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan University, Kunming, Yunnan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Psychiatry, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Xu
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: limingkiz@gmail.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3
keywords: Association; Expression; IRF3; Schizophrenia; eQTL