Association of six polymorphisms of the <i>NOTCH4</i> gene with schizophrenia in the Japanese population

Tochigi, Mamoru; Zhang, Xuan; Umekage, Tadashi; Ohashi, Jun; Kato, C.; Marui, Tetsuya; Otowa, Takeshi; Hibino, Hiroki; Otani, Toshiyuki; Kohda, Kazuhisa; Liu, Shuzheng; Kato, Nobuo; Tokunaga, Katsushi; Sasaki, Tsukasa

doi:10.1002/ajmg.b.30010

Cited by 15 publications

(19 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, subsequent studies using mainly the same markers failed to replicate the initial findings [McGinnis et al, 2001;Sklar et al, 2001;Fan et al, 2002;Tochigi et al, 2004]. Nor did a meta-analysis of the association studies of these five markers find a significant association [Glatt et al, 2005].…”

Section: Introductionmentioning

confidence: 69%

Association study between the TNXB locus and schizophrenia in a Japanese population

Tochigi

Zhang

Ohashi

et al. 2006

American J of Med Genetics Pt B

Self Cite

View full text Add to dashboard Cite

The chromosome 6p21-24 region, which contains the human leukocyte antigen (HLA) region, has been suggested as an important locus for a susceptibility gene for schizophrenia. Recently, a significant association between schizophrenia and the TNXB locus, located immediately telomeric of the NOTCH4 locus in the HLA region, was observed. Few studies have further investigated the region in schizophrenia. In the present study, we investigated the region in a Japanese population. Subjects included 241 patients with schizophrenia and 290 controls. Twenty-six single nucleotide polymorphisms (SNPs) and the corresponding haplotypes were analyzed. As a result, exactly the same SNPs in the TNXB locus (rs1009382 and rs204887) as in the previous study were associated with schizophrenia (P = 0.034 and 0.034, respectively, uncorrected). A SNP (rs2071287) in the NOTCH4 locus and haplotype around it were also suggested to associate with the disease, consistent with another previous study (P = 0.041 and permutation P = 0.024, respectively, uncorrected). Although these associations became insignificant after Bonferroni correction, the findings might provide support for the association of the TNXB locus or its adjacent region of the NOTCH4 locus with schizophrenia.

show abstract

Section: Introductionmentioning

confidence: 69%

Association study between the TNXB locus and schizophrenia in a Japanese population

Tochigi

Zhang

Ohashi

et al. 2006

American J of Med Genetics Pt B

Self Cite

View full text Add to dashboard Cite

show abstract

“…In an initial study, the NOTCH4 locus was found to be associated with schizophrenia in a British population [Wei and Hemmings, 2000]. This finding appears to be supported by several independent studies [Cichon et al, 2001;Klempan et al, 2001;Anttila et al, 2003Anttila et al, , 2004Skol et al, 2003;Takahashi et al, 2003;Luo et al, 2004;Prasad et al, 2004;Wang et al, 2005] although some others have failed to replicate it [Imai et al, 2001;McGinnis et al, 2001;Sklar et al, 2001;Ujike et al, 2001;Fan et al, 2002;Carmine et al, 2003;Kaneko et al, 2004;Tochigi et al, 2004]. The replication work was designed to apply either a population-based study or a family-based study, or both, among different populations.…”

Section: Introductionmentioning

confidence: 89%

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

Wang

Wei²,

Zhang

et al. 2006

American J of Med Genetics Pt B

Self Cite

View full text Add to dashboard Cite

This work reviewed all the reports on the NOTCH4 gene in schizophrenia, which have been published since the gene was found to be associated with illness among a British population in 2000. The results from independent studies were inconsistent. Allelic heterogeneity, clinical diagnosis, ethnical backgrounds, and linkage disequilibrium (LD) structures in the human genome may be major reasons for poor replication. A couple of studies suggested that the NOTCH4 gene could play a role in a subgroup of the disease, such as early-onset schizophrenia and negative symptoms. A single study revealed a weak association of the NOTCH4 gene with frontal lobe brain volumes and a strong association with frontal lobe cognitive performance. A meta-analysis showed stronger evidence of the NOTCH4 association in family-based studies than in case-control studies. In a previous study, we found that rs520692, a single nucleotide polymorphism (SNP) at the NOTCH4 locus, was associated with schizophrenia in a Chinese population. In the present study, we applied a large sample size to re-evaluate our initial findings and then confirmed the rs520692 association with illness. The pairwise measures did not show strong LD between paired SNPs although the SNPs tested are located within a 34-kb region, suggesting that LD within the NOTCH4 gene has been broken rapidly by historical recombination in the Chinese population. Taken together, the NOTCH4 gene may be associated with schizophrenia but how the gene contributes to the etiology of the illness needs a further investigation.

show abstract

“…Alagille syndrome; patients with JAG1 mutations display variable phenotypes in bile duct paucity, cardiac defects (including tetralogy of Fallot), posterior embryotoxon, spine defects (including butterfly vertebrae) and deafness (Bauer et al, 2010;Colliton et al, 2001;Crosnier et al, 1999;Crosnier et al, 2001;Eldadah et al, 2001;Heritage et al, 2002;Heritage et al, 2000;Krantz et al, 1998;Krantz et al, 1999;Li et al, 1997;Oda et al, 2000;Oda et al, 1997;Raas-Rothschild et al, 2002;Ropke et al, 2003;Stankiewicz et al, 2001;Warthen et al, 2006) LFNG Spondylocostal dysostosis (axial skeleton segmentation and growth disorder) (Sparrow et al, 2006) MAML2 Mucoepidermoid carcinoma, secondary acute myeloid leukemia (Conkright et al, 2003;Enlund et al, 2004;Tonon et al, 2003) NOTCH1 (Joutel et al, 1997a;Joutel et al, 2004;Joutel et al, 1997b;Oberstein et al, 1999) Skol et al, 2003;Tochigi et al, 2004;Wei and Hemmings, 2000) In addition to the canonical ligands mentioned above, a multitude of non-canonical ligands (reviewed by D'Souza et al, 2010) can activate or inhibit Notch signaling. An interesting example of a non-canonical ligand is Delta-like homolog 1/2 (Dlk1/2), which is structurally similar to the Dll ligands but lacks a DSL domain.…”

Section: Jag1mentioning

confidence: 99%

Notch signaling: simplicity in design, versatility in function

2011

View full text Add to dashboard Cite

Notch signaling is evolutionarily conserved and operates in many cell types and at various stages during development. Notch signaling must therefore be able to generate appropriate signaling outputs in a variety of cellular contexts. This need for versatility in Notch signaling is in apparent contrast to the simple molecular design of the core pathway. Here, we review recent studies in nematodes, Drosophila and vertebrate systems that begin to shed light on how versatility in Notch signaling output is generated, how signal strength is modulated, and how cross-talk between the Notch pathway and other intracellular signaling systems, such as the Wnt, hypoxia and BMP pathways, contributes to signaling diversity.Key words: Cis-inhibition, Delta-like, Signaling diversity, Jagged, Notch, Notch intracellular domain Introduction Cells need to sense cues from their extracellular environment and integrate this information into appropriate developmental or physiological responses. Although there are a number of mechanisms that relay information from the exterior of the cell to the interior, a relatively small set of highly evolutionarily conserved signaling pathways stand out as playing particularly crucial roles in this transmission of information. In this roster of 'elite' intracellular signaling mechanisms are the Wnt pathway, the sonic hedgehog (Shh) pathway, the bone morphogenetic protein/transforming growth factor  (BMP/TGF) pathway, phosphatidylinositol 3-kinase/thymoma viral proto-oncogene (PI3K/AKT) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, and, the subject of this review, the Notch signaling pathway. Each of these pathways converts information about the concentration of extracellular ligands into specific transcriptional responses in the nucleus. In most cases, the signaling mechanism consists of the 'core' signaling pathway, i.e. the minimal set of protein components required for transducing the signal, and a more elaborate set of 'auxiliary' proteins, which, in various ways, impinge upon the core pathway and modify the signal but are not intrinsically necessary for relaying the signal.Among these highly conserved pathways (Gazave et al., 2009;Richards and Degnan, 2009), the Notch signaling pathway scores highly with regard to simplicity in molecular design, as it contains only a small number of core signaling components (Fig. 1). Despite this, Notch signaling affects cell differentiation decisions not only across a wide spectrum of metazoan species, but also across a broad range of cell types in a single organism and at different steps during cell lineage progression. The pleiotropic actions of Notch in different cell types and organs have recently been reviewed and are summarized in Table 1. In keeping with its important role in many cell types, the mutation of Notch genes leads to diseases in various organs and tissues (Table 2). These studies highlight the fact that the Notch pathway must be able to elicit appropriate responses in many spatially and temporally...

show abstract

Association of six polymorphisms of the NOTCH4 gene with schizophrenia in the Japanese population

Cited by 15 publications

References 18 publications

Association study between the TNXB locus and schizophrenia in a Japanese population

Association study between the TNXB locus and schizophrenia in a Japanese population

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

Notch signaling: simplicity in design, versatility in function

Contact Info

Product

Resources

About