Association evidence of schizophrenia with distal genomic region of NOTCH4 in Taiwanese families

Liu, Chi-Min; Liu, Y.-L.; Fann, Cathy S.J.; Chen, W. J.; Yang, Wen-Jen; Ouyang, Wen‐Chen; Chen, C.-Y.; Jou, Yuh–Shan; Hsieh, Ming H.; Liu, S.-K.; Hwang, Tzung‐Jeng; Faraone, Stephen V.; Tsuang, Ming T.

doi:10.1111/j.1601-183x.2006.00276.x

Cited by 12 publications

(10 citation statements)

References 44 publications

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“…The lack of strength in association called for additional large family‐based studies utilizing haplotype‐tagging SNPs to identify NOTCH4 genetic risk variants. After this meta‐analysis we conducted an independent family‐based association study with 218 nuclear families multiply affected with schizophrenia recruited from hospitals across Taiwan [Liu et al, 2007]. This analysis adopted the systematic approach of utilizing haplotype‐tagging SNPs to test for association in this large family sample, as the prior work had suggested.…”

Section: Initial Identification Of Notch4 As a Schizophrenia Candidatmentioning

confidence: 99%

A re‐review of the association between the NOTCH4 locus and schizophrenia

Shayevitz

Cohen

Faraone

et al. 2012

American J of Med Genetics Pt B

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NOTCH4 has long been identified as a candidate susceptibility gene for schizophrenia, but the collective body of genetic association studies of this gene has been less than conclusive. Recently a variant in NOTCH4 was implicated as one of the most reliably associated polymorphisms observed in a genome-wide association scan of the disorder, and the collective evidence for this polymorphism now surpasses criteria for genome-wide significance. To place these developments in context, we now summarize the initial work identifying NOTCH4 as a candidate gene for schizophrenia. The results of the genome-wide association studies that have confirmed this as a risk gene, and novel bioinformatics analyses that reveal potential functional profiles of the most likely risk-conferring polymorphisms. These analyses suggest that the NOTCH4 polymorphisms most strongly associated with schizophrenia exert their effects on susceptibility by altering the efficiency and/or alternative splicing of Notch4 transcripts. Further experimental evidence should be pursued to clarify the NOTCH4-regulated molecular and cellular phenotypes of relevance to the disorder, and the functional consequences of the implicated polymorphisms in the gene.

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Section: Initial Identification Of Notch4 As a Schizophrenia Candidatmentioning

confidence: 99%

A re‐review of the association between the NOTCH4 locus and schizophrenia

Shayevitz

Cohen

Faraone

et al. 2012

American J of Med Genetics Pt B

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“…Furthermore, rs2071287 and rs3131296, which display very strong LD with each other, were identified as the SNPs that are most likely to be functionally relevant to SCZ etiology, suggesting that it is necessary to determine the association of rs2071287 with SCZ [ 12 , 13 ]. Another SNP, rs204993, was found to be significantly associated with SCZ through a family-based association study of 218 Taiwan nuclear families [ 14 ]. To date, few studies have investigated the association of NOTCH4 with SCZ in the Chinese population, particularly regarding the SNPs rs2071287 and rs204993.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Fan

et al. 2015

BioMed Research International

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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.

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“…Subsequent studies also confirmed the relationship between schizophrenia and NOTCH4 polymorphisms, including microsatellite (Glatt et al, 2005) and single nucleotide polymorphisms (SNPs) (e.g., rs520692, rs3131296, and rs2071287) (Ikeda et al, 2013;Tochigi et al, 2007;Wang et al, 2006). 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).…”

Section: Introductionmentioning

confidence: 91%

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

Xie

Zhang

et al. 2020

Preprint

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Background Schizotypal traits are considered as heritable traits and the endophenotype for schizophrenia. A common variant in NOTCH4 gene, rs204993, has been linked with schizophrenia, but the neural underpinnings are largely unknown. Methods In present study, we compared the difference of brain function between different genotype of rs204993 and its relationship with schizotypal traits among 402 Chinese Han healthy volunteers. The brain function was evaluated with functional connectivity strength (FCS) using resting-state functional magnetic resonance image (rs-fMRI). The schizotypal traits were measured by the schizotypal personality questionnaire (SPQ). Results Our results suggested that the carriers with AA genotype showed reduced FCS in left occipital cortex than the carriers with AG and GG genotype and the carriers with AG genotype showed reduced FCS in left occipital cortex than the carriers with GG genotype. The FCS values in the left occipital lobe were negatively associated with the SPQ scores and its subscale scores within the carriers with GG genotype, but not within the carriers with AA or AG genotype. Conclusions Our results suggested that the common variant in NOTCH4 gene, rs204993, modulate the function of occipital cortex, which may contribute to the schizotypal traits. These findings provided insight for genetic effect on schizotypal traits and its potential neural substrate.

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Association evidence of schizophrenia with distal genomic region of NOTCH4 in Taiwanese families

Cited by 12 publications

References 44 publications

A re‐review of the association between the NOTCH4 locus and schizophrenia

A re‐review of the association between the NOTCH4 locus and schizophrenia

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

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

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