TCF4 gene polymorphism is associated with cognition in patients with schizophrenia and healthy controls

Cognitive deficits have been identified as an important core feature of schizophrenia. Single nucleotide polymorphisms in the transcription factor 4 (TCF4) gene have been reported to be involved in the susceptibility to schizophrenia and be significantly related to cognitive deficits of schizophrenia and controls. This study examines whether the TCF4 rs2958182 polymorphism influences cognitive functions in chronic schizophrenia and controls.

The presence of the TCF4 rs2958182 was determined in 976 patients and 420 controls using a case-control design. We assessed all the patients' psychopathology using the Positive and Negative Syndrome Scale (PANSS). Cognition was assessed in 777 patients and 399 controls by using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

There were marginally significant differences in the TCF4 rs2958182 allelic and genotypic distributions between patients and controls (χ2 = 3.48, p = 0.062 and χ2 = 0.036, p = 0.036, respectively). Cognitive test scores were significantly lower in patients than in controls on all scales (all p < 0.001) except for the visuospatial/constructional index (p > 0.05). There were significant genotype effects on delayed memory score (p = 0.013), the RBANS total score (p = 0.028) and language score (p = 0.034). Further analysis showed that the language score significantly differed according to the genotypic groups (A/A+T/A group versus T/T group) (p = 0.007) in patients but not in controls (p > 0.05), and the delayed memory score also significantly differed according to the genotypic groups (A/A+T/A group versus T/T group) (p = 0.021) in controls but not in patients (p > 0.05).

This study found that the A allele of the TCF4 rs2958182 polymorphism was the risk allele of schizophrenia, and was associated with lower cognitive performance in language in schizophrenia and delayed memory in controls. In contrast, the T allele of this polymorphism was found to be the schizophrenia risk allele in another study in Han Chinese people.