Five NOTCH4 polymorphisms show weak evidence for association with schizophrenia: evidence from meta-analyses

Glatt, Stephen J.; Wang, Richard S.; Yeh, Yu-Chi; Tsuang, Ming T.; Faraone, Stephen V.

doi:10.1016/j.schres.2004.07.015

Cited by 24 publications

(18 citation statements)

References 25 publications

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“…The heterogeneity among the studies suggests that some unknown factor may lead to the association of several SNPs with the disease in some contexts but not in others. 29 The effect of SNPs on schizophrenia risk may be moderated by sample or study characteristics not addressed in the present analyses. In three family-based association studies, we did not find significant evidence for association of the SNPs rs3916967 and rs2391191 with schizophrenia.…”

Section: Discussionmentioning

confidence: 94%

Further evidence for the association between G72/G30 genes and schizophrenia in two ethnically distinct populations

Qin

Wang

et al. 2006

Mol Psychiatry

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Recently, the nested genes G72 and G30 on chromosome 13q32-q33 have been implicated in the etiology of schizophrenia. We genotyped six single-nucleotide polymorphisms (SNPs: rs3916965, rs3916967, rs2391191, rs778294, rs779293 and rs3918342), which span approximately 82.5 kb in the region encompassing the G72/G30 genes in 1176 Han Chinese subjects (588 cases and 588 controls) and 365 Scottish subjects (183 cases and 182 controls). Significant association between an allele of marker rs778293 and schizophrenia was found in our Chinese samples (P = 0.0013), and was replicated in the Scottish samples (P = 0.022). LD analysis revealed that four SNPs between rs3916965 and rs778294 were in LD, called block I, and the two distal SNPs (rs778293 and rs3918342) constituted a block II in both the Chinese and Scottish samples. We selected one SNP from each block (rs778294 from block I and rs778293 from block II), and then analyzed the haplotypes. A significant difference was observed for the common haplotype GC in the Chinese sample (P = 0.0145), and was replicated in the Scottish sample (P = 0.003). On meta-analysis, we separately analyzed the studies in Asian and European populations because of significant heterogeneity in the homogeneity test. We found a statistically significant association between rs778293 and schizophrenia in Asian populations, but no difference was found between cases and controls in the European populations. Overall, our data give further support to the existing evidence that G72/G30 genes are involved in conferring susceptibility to schizophrenia.

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Section: Discussionmentioning

confidence: 94%

Further evidence for the association between G72/G30 genes and schizophrenia in two ethnically distinct populations

Qin

Wang

et al. 2006

Mol Psychiatry

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“…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]. Zhang et al [2004], however, observed an association of rs520692; not one of the five original markers employed by Wei and Hemmings [2000], in 141 Han Chinese trios (P ¼ 0.017).…”

Section: Introductionmentioning

confidence: 94%

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

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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.

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“…12 Population heterogeneity, phenotypic heterogeneity, interweaving diagnostic criteria and misclassification, overestimated risk in the initial study, small sample size, influence of multiple loci (causal heterogeneity) and genetic-environmental interactions are among the indicated causes for the failure of replication of association studies. 5,7,12,13 Some of the strongest causative candidates to date are considered to be DISC1, DTNBP1, COMT, NRG1 and RGS4.…”

Section: Schizophrenia (F20 International Classification Of Diseasesmentioning

confidence: 99%

Case–control association study of 59 candidate genes reveals the DRD2 SNP rs6277 (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian population

et al. 2009

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The development of molecular psychiatry in the last few decades identified a number of candidate genes that could be associated with schizophrenia. A great number of studies often result with controversial and non-conclusive outputs. However, it was determined that each of the implicated candidates would independently have a minor effect on the susceptibility to that disease. Herein we report results from our replication study for association using 255 Bulgarian patients with schizophrenia and schizoaffective disorder and 556 Bulgarian healthy controls. We have selected from the literatures 202 single nucleotide polymorphisms (SNPs) in 59 candidate genes, which previously were implicated in disease susceptibility, and we have genotyped them. Of the 183 SNPs successfully genotyped, only 1 SNP, rs6277 (C957T) in the DRD2 gene (P¼0.0010, odds ratio¼1.76), was considered to be significantly associated with schizophrenia after the replication study using independent sample sets. Our findings support one of the most widely considered hypotheses for schizophrenia etiology, the dopaminergic hypothesis.

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Five NOTCH4 polymorphisms show weak evidence for association with schizophrenia: evidence from meta-analyses

Cited by 24 publications

References 25 publications

Further evidence for the association between G72/G30 genes and schizophrenia in two ethnically distinct populations

Further evidence for the association between G72/G30 genes and schizophrenia in two ethnically distinct populations

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

Case–control association study of 59 candidate genes reveals the DRD2 SNP rs6277 (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian population

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