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.
These results imply that PPI might be modulated by four genotypes - COMT rs4680 (primarily in males), GRIK3 rs1027599, TCF4 rs9960767, and PRODH rs385440 - indicating a role of these gene variations in the development of early information processing deficits in schizophrenia.
The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value = 2.57×10⁻⁴) and rs9960767 (p-value = 6.23×10⁻⁴).
Single nucleotide polymorphisms in TCF4 gene have been consistently associated with schizophrenia in genome wide association studies, including the C allele of rs9960767.
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).
We therefore investigated the impact of the schizophrenia susceptibility gene TCF4 (rs9960767) on sensorimotor gating of the ASR in healthy humans and in patients with a schizophrenia spectrum disorder.
Thus, we hypothesized that the disease-associated C allele of the rs9960767 polymorphism of the TCF4 gene led to impaired VDM functioning in schizophrenia patients.
Here, we generated two novel mouse models of PTHS, one that mimics the most common pathogenic <i>TCF4</i> point mutation (human R580W, mouse R579W) and one that deletes three pathogenic arginines, and explored phenotypes of these lines alongside models of pan-cellular or CNS-specific heterozygous <i>Tcf4</i> disruption.
The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value = 2.57×10⁻⁴) and rs9960767 (p-value = 6.23×10⁻⁴).
Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction.