Association of theNOTCH4Gene Polymorphism rs204993 with Schizophrenia in the Chinese Han Population

Abstract

NOTCH4 regulates signaling pathways associated with neuronal maturation, a process involved in the development and patterning of the central nervous system. The NOTCH4 gene has also been identified as a possible susceptibility gene for schizophrenia (SCZ). The objective of this study was to examine the relationship between NOTCH4 polymorphisms and SCZ in the Chinese Han population. The rs2071287 and rs204993 polymorphisms of the NOTCH4 gene were analyzed in 443 patients with SCZ and 628 controls of Han Chinese descent. Single SNP allele-, genotype-, and gender-specific associations were analyzed using different models (i.e., additive, dominant, and recessive models). This association study revealed that the rs204993 polymorphism is significantly associated with susceptibility for SCZ and that the AA genotype of rs204993 is associated with a higher risk for SCZ (P = 0.027; OR = 1.460; 95% CI, 1.043–2.054). Our data are consistent with those obtained in previous studies that suggested that rs204993 is associated with SCZ and that the AA genotype of rs204993 demonstrates a higher risk. Further large-scale association analyses in Han Chinese populations are warranted.

Common variant of NOTCH4 gene modulate functional connectivity of occipital cortex and its relationship with schizotypal traits

“…Table 1 presented the demographic, genetic, and behavioral data for participants included in the final analysis. The genotype distribution of NOTCH4 rs204993 in current study (AA = 142, AG = 188, and GG = 72) was consistent with the previous report of variation of this gene in healthy Chinese Han population (Zhang et al, 2015a). There were no significant differences in gender, educational years and age between genotype groups.…”

“…Recently, study among 218 Taiwanese families has found another SNP, rs204993 with significant relationship with schizophrenia through testing the association of the entire genomic region of NOTCH4 (Liu et al, 2007). Specially, the AA genotype of rs204993 was associated with a higher risk for schizophrenia in the Chinese Han population (Zhang et al, 2015a). As the intermediary role of brain function for the genetic effect on schizophrenia, there may be significant differences of brain function in schizophrenia-related region between distinct genotypes of rs204993.…”

A common variant of the NOTCH4 gene modulates functional connectivity of the occipital cortex and its relationship with schizotypal traits

“…Table 1 shows the demographic, genetic, and behavioral data for participants included in the final analysis. The genotype distribution of NOTCH4 rs204993 in the current study (AA = 142, AG = 188, and GG = 72) was consistent with a previous report of variations of this gene in the healthy Chinese Han population [16]. Genotype groups did not significantly deviate from Hardy-Weinberg equilibrium (χ2 = 0.505, p = 0.477).…”

“…It is worth noting that we found that the FCS of the occipital cortex was degressive in sequences of the GG, AG, and AA genotype groups that suggest an additive effect of rs204993. This is not in complete agreement with a recessive effect revealed by the previous results that the AA genotype of rs204993 is associated with a higher risk for schizophrenia in the Chinese Han population [16]. The difference between schizophrenia and schizotypal traits may explain this discrepancy.…”

“…Recently, a study among 218 Taiwanese families reported another SNP, rs204993 with a significant relationship with schizophrenia, found by testing the association of the entire genomic region of NOTCH4 [15]. Specially, the AA genotype of rs204993 was associated with a higher risk for schizophrenia in the Chinese Han population [16].…”