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).
At present no strong evidence exists that large repeat alleles at either SEF2-1B or ERDA1 are involved in the etiology of schizophrenia or bipolar disorder.
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.
These include ZNF804A, TCF4 and NRGN, which contain common variants that weakly increase schizophrenia susceptibility, and NRXN1, in which rare copy number variants have a greater impact on schizophrenia risk.
Our results confirm that common risk factors in the major histocompatibility complex region and TCF4 gene are associated with schizophrenia in Han Chinese, but our results fail to show an association with SNP rs12807809 in the NRGN gene.
Sensorimotor gating is modulated by TCF4 genotype, indicating an influential role of TCF4 gene variations in the development of early information-processing deficits in schizophrenia.
We conclude that association between schizophrenia and TCF4 is not mediated by a relatively common non-synonymous variant, or by a variant that alters mRNA expression as measured in adult human brain.
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.
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).
Risk genes associated with SZ at genome wide significance level (p value<7.2 × 10(-8)) include zinc finger binding protein 804A (ZNF804A), major histocompatibility (MHC) region on chromosome 6, neurogranin (NRGN) and transcription factor 4 (TCF4).
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.