Genetic Variability of TCF4 in Schizophrenia of Southern Chinese Han Population: A Case-Control Study.

Jingwen Yin,Jiawu Fu,Juda Lin,Dongjian Zhu,Haifeng Yan,Chunmei Liang,Xia Zhou,Xudong Luo,Susu Xiong,Keshen Li,Xusan Xu,Guoda Ma,Huajun Yu,Dong Lv,You Li,Yajun Wang,Bin Zhao,Zhongqiu Lin ,Zhongmin Dai ,Xin Wen

doi:10.3389/fgene.2019.00513

Abstract

Objective: Schizophrenia is thought to be a neurodevelopmental disorder. As a key regulator in the development of the central nervous system, transcription factor 4 (TCF4) has been shown to be involved in the pathogenesis of schizophrenia. The aim of our study was to assay the association of TCF4 single nucleotide polymorphisms (SNPs) with schizophrenia and the effect of these SNPs on phenotypic variability in schizophrenia in Southern Chinese Han Population.Methods: Four SNPs (rs9960767, rs2958182, rs4309482, and rs12966547) of TCF4 were genotyped in 1137 schizophrenic patients and 1035 controls in a Southern Chinese Han population using the improved multiplex ligation detection reaction (iMLDR) technique. For patients with schizophrenia, the severity of symptom phenotypes was analyzed by the five-factor model of the Positive and Negative Symptom Scale (PANSS). Cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) scale.Results: The results showed that the genotypes and alleles of the three SNPs (rs2958182, rs4309482, and rs12966547) were not significantly different between the control group and the case group (all P > 0.05). rs9960767 could not be included in the statistics for the extremely low minor allele frequency. However, the genotypes of rs4309482 shown a potential risk in the positive symptoms (P = 0.04) and excitement symptoms (P = 0.04) of the five-factor model of PANSS, but not survived in multiple test correction. The same potential risk was shown in the rs12966547 in positive symptoms of the PANSS (P = 0.03).Conclusion: Our results failed to find the associations of SNPs (rs2958182, rs4309482, and rs12966547) in TCF4 with schizophrenia in Southern Chinese Han Population.

Highlights

Schizophrenia is thought to be a highly heritable disease with a genetic architecture arising from the subtle effect of multiple risk genes (Wang et al, 2017)
The results showed that the genotypes and alleles of the three single nucleotide polymorphisms (SNPs) were not significantly different between the control group and the case group. rs9960767 could not be included in the statistics for the extremely low minor allele frequency
Our results failed to find the associations of SNPs in transcription factor 4 (TCF4) with schizophrenia in Southern Chinese Han Population

Summary

Introduction

Schizophrenia is thought to be a highly heritable disease with a genetic architecture arising from the subtle effect of multiple risk genes (Wang et al, 2017). The “accumulation” of dysregulation events in susceptibility genes leading to dysfunction in the nervous system results in the phenotypic heterogeneity of schizophrenia, including positive symptoms, negative symptoms, and cognitive dysfunction (Takahashi, 2013). TCF4, a transcription factor involved in the development of the nervous system, is found to be a highly plausible candidate for contributing to schizophrenia (Lennertz et al, 2011). Corresponding results in clinical studies suggested a critical effect of TCF4 in several phenotypes of schizophrenia, including age at onset, sensorimotor gating, negative symptoms, cognitive function and MRI-measured brain structure (Albanna et al, 2014; Hui et al, 2015; Chow et al, 2016; Alizadeh et al, 2017). TCF4 has been identified as a direct target of schizophrenia-associated pivotal factor miR-137, suggesting a particular susceptibility whereby TCF4 could be involved in the gene regulatory networks underlying schizophrenia (Yin et al, 2014; Xia et al, 2018)

Methods

Results

Conclusion