Polymorphisms of the TCF4 gene are associated with the risk of schizophrenia in the Han Chinese

Am J Med Genet B Neuropsychiatr Genet. 2016 Dec;171(8):1006-1012. doi: 10.1002/ajmg.b.32449. Epub 2016 Apr 22.

Abstract

Schizophrenia (SCZ) is a complex and severe mental disorder with highly heritability (80%). Several large genome-wide association studies have identified that the transcription factor 4 (TCF4) polymorphisms were strongly associated with SCZ. Therefore, the present study was to replicate the potential relationships between the TCF4 polymorphisms and SCZ. Furthermore, the study also investigated whether other variants were associated with SCZ in the Han Chinese. We conducted a case-control study including 499 patients and 500 healthy controls. Five SNPs were successfully genotyped and evaluated the association with SCZ by using χ2 test and genetic model analysis. We found that the genotype "AG" of rs9320010 and "GA" of rs7235757 decreased SCZ risk (OR = 0.70, 95%CI = 0.50-0.99, P = 0.041; OR = 0.69, 95%CI = 0.49-0.97, P = 0.034, respectively). In the genetic model analysis, we also observed that the allele "A" of rs9320010 and "G" of rs7235757 were inversely related with the risk of SCZ in the dominant model (OR = 0.72, 95%CI = 0.52-0.98, P = 0.039; OR = 0.69, 95%CI = 0.50-0.96, P = 0.025, respectively). Further interaction and stratification analysis suggested that rs1452787 was notably correlated with increased SCZ risk in males (OR = 2.77, 95%CI = 1.43-5.35, P = 0.002). Our study indicated that rs9320010, rs7235757, and rs1452787 were prominently associated with SCZ. Further studies are required to verify our findings and focus on determining the biological functions of the SNPs. © 2016 Wiley Periodicals, Inc.

Keywords: Han Chinese; Schizophrenia; TCF4; case-control; single nucleotide polymorphism.

MeSH terms

  • Adult
  • Alleles
  • Asian People / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Case-Control Studies
  • China
  • Ethnicity / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Schizophrenia / genetics*
  • Transcription Factor 4
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors