For this purpose, we genotyped the schizophrenia-associated risk variants within zinc-finger protein 804A (ZNF804A), transcription-factor 4 and neurogranin in a large dyslexia case-control sample.
However, the results from our association and power analyses suggest that further research into the possible involvement of rare TCF4 sequence variants in schizophrenia risk is warranted by the assessment of larger cohorts with higher statistical power to identify rare variant associations.
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.
These results imply that PPI might be modulated by four genotypes - COMT rs4680 (primarily in males), GRIK3 rs1027599, TCF4rs9960767, and PRODH rs385440 - indicating a role of these gene variations in the development of early information processing deficits in schizophrenia.
P50 suppression was significantly decreased in carriers of schizophrenia risk alleles of the TCF4 polymorphisms rs9960767, rs10401120rs, rs17597926, and 17512836 (P < 0.0002-0.00005).
Single nucleotide polymorphisms in TCF4 gene have been consistently associated with schizophrenia in genome wide association studies, including the C allele of rs9960767.
Importantly, we found that genes harboring de novo mutations in schizophrenia (P = 5.3 × 10-7), ASD (P = 2.5 × 10-4), and ID (P = 7.6 × 10-3) were also enriched among TCF4 targets.
Our results suggest that a SCZ risk variant in TCF4 is associated with neurophysiologic traits thought to index attention and working memory abnormalities in psychotic disorders.
Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
We observed no increase in frequency of larger alleles (>37 repeats) in affected individuals at SEF2-1B (BPAD: P=0.95, n= 100; SCZ: P=0.61, n=97) or at ERDA1 (BPAD: P= 0.4, n = 101; SCZ: P= 0.05, n = 151, with larger alleles more frequent in controls).
Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder.
TCF4 is involved in neurodevelopment, and intergenic and intronic variants in or close to the TCF4 gene have been associated with susceptibility to schizophrenia.
Here, we replicated the four European GWAS hits, miR-137-rs1625579 and three of its validated target gene loci SNPs (ZNF804a-rs1344706, CACNA1C-rs4765905 and TCF4-rs9960767) by genotyping in 2074 samples (schizophrenia cases-1005; controls-1069) from South Indian Population.
The TCF4 gene is also a risk factor with highly significant linkage to schizophrenia, presumably via overexpression of the TCF4 gene product in the central nervous system.