TCF4 gene polymorphism and cognitive performance in patients with first episode psychosis

Albanna, Ammar; Choudhry, Zia; Harvey, Philippe‐Olivier; Fathalli, Ferid; Cassidy, Clifford; Sengupta, Sarojini M.; Iyer, Srividya N.; Rho, Aldanie; Lepage, Martín; Malla, Ashok; Joober, Ridha

doi:10.1016/j.schres.2013.10.038

Cited by 25 publications

(19 citation statements)

References 45 publications

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“…The authors reported that carriers of the rs9960767 C allele performed worse in the cognitive domains of "reasoning and problem solving" and "speed of processing" adumbrating that TCF4 polymorphisms might contribute also to deficits in higher cognitive function in schizophrenia patients [129] In a lymphocyte-based gene expression study in healthy Mexican Americans, it has been recently shown that peripheral expression of TCF4 -among seven further genes (IGFBP3, LRRN3, CRIP2, SCD, IDS, GATA3, and HN1) -predicted cortical grey matter thickness measured with magnet resonance tomography [130]. Notably, TCF4 expression was correlated particularly with grey matter thickness in the prefrontal cortex.…”

Section: Tcf4 Information Processing and Cognition: Human Studiesmentioning

confidence: 99%

Transcription factor 4 (TCF4) and schizophrenia: integrating the animal and the human perspective

Quednow

Brzózka

Rossner

2014

Cell. Mol. Life Sci.

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Schizophrenia is a genetically complex disease considered to have a neurodevelopmental pathogenesis and defined by a broad spectrum of positive and negative symptoms as well as cognitive deficits. Recently, large genome-wide association studies have identified common alleles slightly increasing the risk for schizophrenia. Among the few schizophrenia-risk genes that have been consistently replicated is the basic Helix-Loop-Helix (bHLH) transcription factor 4 (TCF4). Haploinsufficiency of the TCF4 (formatting follows IUPAC nomenclature: TCF4 protein/protein function, Tcf4 rodent gene cDNA mRNA, TCF4 human gene cDNA mRNA) gene causes the Pitt-Hopkins syndrome-a neurodevelopmental disease characterized by severe mental retardation. Accordingly, Tcf4 null-mutant mice display developmental brain defects. TCF4-associated risk alleles are located in putative coding and non-coding regions of the gene. Hence, subtle changes at the level of gene expression might be relevant for the etiopathology of schizophrenia. Behavioural phenotypes obtained with a mouse model of slightly increased gene dosage and electrophysiological investigations with human risk-allele carriers revealed an overlapping spectrum of schizophrenia-relevant endophenotypes. Most prominently, early information processing and higher cognitive functions appear to be associated with TCF4 risk genotypes. Moreover, a recent human study unravelled gene × environment interactions between TCF4 risk alleles and smoking behaviour that were specifically associated with disrupted early information processing. Taken together, TCF4 is considered as an integrator ('hub') of several bHLH networks controlling critical steps of various developmental, and, possibly, plasticity-related transcriptional programs in the CNS and changes of TCF4 expression also appear to affect brain networks important for information processing. Consequently, these findings support the neurodevelopmental hypothesis of schizophrenia and provide a basis for identifying the underlying molecular mechanisms. AbstractSchizophrenia is a genetically complex disease considered to have a neurodevelopmental pathogenesis and defined by a broad spectrum of positive and negative symptoms as well as cognitive deficits.Recently, large genome-wide association studies have identified common alleles slightly increasing the risk for schizophrenia. Among the few schizophrenia-risk genes that have been consistently replicated is the basic Helix-Loop-Helix (bHLH) transcription factor 4 (TCF4 behaviour that were specifically associated with disrupted early information processing. Taken together, TCF4 is considered as an integrator ('hub') of several bHLH networks controlling critical steps of various developmental and possibly also plasticity related transcriptional programs in the CNS and changes of TCF4 expression appear to affect brain networks important for information processing.Consequently, these findings support the neurodevelopmental hypothesis of schizophrenia and provide a basis to identify the und...

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Section: Tcf4 Information Processing and Cognition: Human Studiesmentioning

confidence: 99%

Transcription factor 4 (TCF4) and schizophrenia: integrating the animal and the human perspective

Quednow

Brzózka

Rossner

2014

Cell. Mol. Life Sci.

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“…It is known to regulate the patterns of differential gene expression required for cell differentiation and neurodevelopment, and to affect the gray matter thickness during cerebral aging [20]. Furthermore, studies have identified a key role of TCF4 in neurocognition [21] and sensorimotor gating [22], where this gene is specifically implicated in reasoning and problem-solving deficits in schizophrenia patients [20]. …”

Section: Introductionmentioning

confidence: 99%

Genetic Association of TCF4 and AKT1 Gene Variants with the Age at Onset of Schizophrenia

Chow

Tee²,

Yong³

et al. 2016

Neuropsychobiology

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Background: Age at onset (AAO) is a known prognostic indicator for schizophrenia and is hypothesized to correlate with cognition and symptom severity. TCF4 and AKT1 are schizophrenia risk genes involved in cognitive functions. The current study examined the interactive effects of TCF4 and AKT1 variants with gender, family history of psychiatric disorders and ethnicity on the AAO of schizophrenia. Methods: This study consisted of 322 patients with schizophrenia meeting the DSM-IV criteria. Six single nucleotide polymorphisms (SNPs) of TCF4 (rs12966547, rs8766, rs2958182, rs9960767, rs10401120 and rs17512836) and seven AKT1 SNPs (rs2498804, rs3803304, rs2494732, rs3730358, rs1130214, rs2498784 and rs3803300) were genotyped using the TaqMan® SNP genotyping-based assays method. The relationship of AAO with each variant was investigated using analyses of covariance. Results: Among the TCF4 variants, rs12966547 (p = 0.024) and rs8766 (p = 0.021) were significantly associated with earlier AAO. We found a lower average AAO in patients with the AA genotype of rs12966547, while the CT genotype of rs8766 was demonstrated to have a protective effect on AAO. For rs8766, there was significant gene × gender interaction (p = 0.012) in influencing AAO. However, these results were not significant after false discovery rate correction. Significant gene × ethnicity interactions were observed to influence AAO (p < 0.05). The Kaplan-Meier curve of the minor AA genotype of rs12966547 displayed a significant trend (p = 0.008) for onset after 19 years of age. Similarly, the minor CC genotype of rs8766 showed a significantly (p = 0.034) lower AAO compared to the TT genotype. Conclusion: Our analyses suggest that individual risk genotypes may influence the risk of schizophrenia in an age-specific manner.

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“…Cognitive tests were also performed on all subjects. AA carriers showed improved performance (P=0.038) in problem solving and reasoning compared with the C risk allele carriers (CC/CA) (18). These studies demonstrated that TCF4 may influence cognitive function and contribute to psychiatric disorders.…”

Section: Genementioning

confidence: 71%

“…The TCF4 genotype was found to modulate sensorimotor gating, which was reduced in C risk allele carriers (17). Albanna et al (18) genotyped TCF4 rs9960767 in 173 patients with first-episode psychosis. Cognitive tests were also performed on all subjects.…”

Section: Genementioning

confidence: 99%

Transcription factor 4 gene rs9960767 polymorphism in bipolar disorder

2016

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Abstract. The transcription factor 4 (TCF4) gene encodes a helix-loop-helix transcription factor protein, which initiates neuronal differentiation and is primarily expressed during nervous system development. The aim of the present study is to investigate the association of the TCF4 rs9960767 polymorphism and bipolar disorder, which is highly heritable. DNA isolation was performed on 95 patients with bipolar disorder and 108 healthy control subjects to examine the TCF4 rs9960767 polymorphism. Genotypic and allelic frequencies were determined using the polymerase chain reaction-restriction fragment length polymorphism method designed in our laboratory. Statistical analysis was performed using χ 2 test within the 95% confidence interval. Odds ratios were calculated and Hardy-Weinberg equilibrium (HWE) was verified for all control subjects and patients. The A allele frequency was 95.8% in the patients and 94.4% in the control subjects, and 4.2% in the patients and 5.6% in the control subjects for the C allele. The genotype frequencies of the TCF4 gene rs9960767 variant were as follows: AA, 91.6% and AC, 8

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TCF4 gene polymorphism and cognitive performance in patients with first episode psychosis

Cited by 25 publications

References 45 publications

Transcription factor 4 (TCF4) and schizophrenia: integrating the animal and the human perspective

Transcription factor 4 (TCF4) and schizophrenia: integrating the animal and the human perspective

Genetic Association of <b><i>TCF4</i></b> and <b><i>AKT1</i></b> Gene Variants with the Age at Onset of Schizophrenia

Transcription factor 4 gene rs9960767 polymorphism in bipolar disorder

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