Association between a TCF4 Polymorphism and Susceptibility to Schizophrenia

Abstract

The basic helix-loop-helix (bHLH) transcription factor 4 (TCF4) had been identified as a susceptibility gene associated with schizophrenia (SCZ) by GWAS, but inconsistent results have been found in other studies. To validate these findings and to reveal the effects of different inheritance models, rs2958182, rs1261085, rs8766, and rs12966547 of the TCF4 gene were genotyped in the Northwest Han Chinese population (448 cases and 628 controls) via a multiplex polymerase chain reaction SNPscan assay. Single SNP, genotype, and association analyses with three different models were performed. We observed genotype and allele distributions of four SNPs that showed nonsignificant associations in the Northwest Han Chinese population. However, published datasets (51,892 cases and 68,498 controls) were collected and combined with our experimental results to ascertain the association of the TCF4 gene SNPs and SCZ, which demonstrated that rs2958182 (P=0.003) was a significant signal based on a systematic meta-analysis. To clarify the biological role of rs2958182, it is important to improve the understanding of the pathophysiology of SCZ.

Genetic Polymorphisms in miR-137 and Its Target Genes, TCF4 and CACNA1C, Contribute to the Risk of Bipolar Disorder: A Preliminary Case-Control Study and Bioinformatics Analysis

“…the results of their study with previously published reports, they found a noteworthy association between TCF4 rs1261084C/T and SCZ susceptibility [78]. Results of an investigation by Hui et al indicated that another SNP in the TCF4 gene, rs2958182A/T, affected SCZ risk and was associated with lower cognitive performance in the language in these patients [79].…”

“…Using multiplex polymerase chain reaction- (PCR-) SNPscan assay, Gao et al genotyped 448 SCZ cases and 628 controls from a northwest Han Chinese population and found no significant link between TCF4 rs1261084C/T and the disease. However, by combining the results of their study with previously published reports, they found a noteworthy association between TCF4 rs1261084C/T and SCZ susceptibility [ 78 ]. Results of an investigation by Hui et al indicated that another SNP in the TCF4 gene, rs2958182A/T, affected SCZ risk and was associated with lower cognitive performance in the language in these patients [ 79 ].…”

Transcription factors in neurodevelopmental and associated psychiatric disorders: A potential convergence for genetic and environmental risk factors

“…TCF4 is known to be intimately related to PTHS (Amiel et al, 2007), and interestingly, in schizophrenia, many altered biological pathways have a significant association with this TF. Since the late 2000s, when the first study associating alterations in TCF4 and schizophrenia was released (Stefansson et al, 2009), several other studies consolidated and demonstrated the relevance of TCF4 in psychotic episodes and bipolar disorder (Gao et al, 2020; Hall et al, 2014; Ripke et al, 2014; Steinberg et al, 2011).…”

Genome-wide association studies-supported rs12966547 variant of the long noncoding RNA LOC105372125 is significantly associated with susceptibility to schizophrenia and bipolar disorder in Han Chinese women

“…no significant differences were observed at the genome level ( P < 10 −8 )] (Moons et al , 2016). Moreover, two studies showed that rs12966547 is not significantly associated with the risk of schizophrenia in the Han Chinese population (Gao et al , 2020; Yin et al , 2019). The genotypic distribution of rs12966547 shows some notable racial differences (based on the HapMap data); for example, the minor allele is A in Caucasians but G in the Chinese.…”