Allelic association of G72/G30 with schizophrenia and bipolar disorder: A comprehensive meta-analysis

Shi, Jiajun; Badner, Judith A.; Gershon, Elliot S.; Liu, Chun Yu

doi:10.1016/j.schres.2007.10.004

Cited by 92 publications

(66 citation statements)

References 58 publications

(82 reference statements)

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“…Genetic association of DAO with schizophrenia has been demonstrated in several (13)(14)(15)(16)(17) but not all (18 -21) linkage and association studies (22). Nevertheless, association studies have identified several single-nucleotide polymorphisms (SNPs) within the gene encoding G72, a putative DAO-interacting protein, which are associated with schizophrenia (14,15,17,23).…”

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confidence: 99%

d-Amino Acid Oxidase Activity Is Inhibited by an Interaction with Bassoon Protein at the Presynaptic Active Zone

Popiolek

Ross

Charych

et al. 2011

Journal of Biological Chemistry

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Schizophrenia is a highly heritable neuropsychiatric disorder affecting ϳ1% of the world's population. Linkage and association studies have identified multiple candidate schizophrenia susceptibility genes whose functions converge on the glutamatergic neurotransmitter system. One such susceptibility gene encoding D-amino acid oxidase (DAO), an enzyme that metabolizes the NMDA receptor (NMDAR) co-agonist D-serine, has the potential to modulate NMDAR function in the context of schizophrenia. To further investigate its cellular regulation, we sought to identify DAO-interacting proteins that participate in its functional regulation in rat cerebellum, where DAO expression is especially high. Immunoprecipitation with DAO-specific antibodies and subsequent mass spectrometric analysis of coprecipitated proteins yielded 24 putative DAO-interacting proteins. The most robust interactions occurred with known components of the presynaptic active zone, such as bassoon (BSN) and piccolo (PCLO). The interaction of DAO with BSN was confirmed through co-immunoprecipitation assays using DAOand BSN-specific antibodies. Moreover, DAO and BSN colocalized with one another in cultured cerebellar granule cells and in synaptic junction membrane protein fractions derived from rat cerebellum. The functional consequences of this interaction were studied through enzyme assay experiments, where DAO enzymatic activity was significantly inhibited as a result of its interaction with BSN. Taking these results together, we hypothesize that synaptic D-serine concentrations may be under tight regulation by a BSN-DAO complex. We therefore predict that this mechanism plays a role in the modulation of glutamatergic signaling through NMDARs. It also furthers our understanding of the biology underlying this potential therapeutic entry point for schizophrenia and other psychiatric disorders.Several lines of evidence, including NMDAR 2 antagonist studies, pharmacological intervention at the glycine modulatory site, postmortem patient brain analysis, and genetic studies, implicate NMDAR hypofunction in schizophrenia etiology (1). One potential approach for restoring NMDAR signaling is to increase the concentration of NMDAR co-agonists, such as D-serine and D-alanine (2-5). Levels of D-serine have been shown to be reduced in the CSF and serum of schizophrenic patients compared with control subjects (6, 7), which may reflect an increase in the activity of D-amino acid oxidase (DAO), the enzyme that catalyzes D-serine and D-alanine degradation (8,9). Supporting this hypothesis are reports of increased DAO activity in schizophrenic patients (10 -12).Genetic association of DAO with schizophrenia has been demonstrated in several (13-17) but not all (18 -21) linkage and association studies (22). Nevertheless, association studies have identified several single-nucleotide polymorphisms (SNPs) within the gene encoding G72, a putative DAO-interacting protein, which are associated with schizophrenia (14,15,17,23).Data from DAO functional knock-out mice provide further s...

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mentioning

confidence: 99%

d-Amino Acid Oxidase Activity Is Inhibited by an Interaction with Bassoon Protein at the Presynaptic Active Zone

Popiolek

Ross

Charych

et al. 2011

Journal of Biological Chemistry

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“…Overall, our data provides further evidence for a positive association between the DAOA locus and schizophrenia and bipolar disorder. A meta-analysis [23] was conducted; combined 18 association articles have shown association between M18 and schizophrenia. This association was not observed in Iran.…”

Section: Discussionmentioning

confidence: 99%

Genetic Overlap Between Affective Disorders: An Association Analysis of M18 and M23 SNPs of DAOA/G72 Gene With Schizophrenia and Bipolar Disorder

Ahmadi

Kazeminezhad

Khajehdin

et al. 2015

Zahedan J Res Med Sci

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Background: Schizophrenia and bipolar disorder are common and often destructive brain disorders. It has generally been assumed that dozens of genes, along with environmental factors, contribute to the development of these diseases. Schizophrenia and bipolar mood disorder affect many families simultaneously. This theme suggests that these disorders have a shared genetic etiology at least to some extent. The DAOA/G72 gene is one of the common loci shared both by schizophrenia and bipolar disorder. The functions of this gene could converge in a pathway of glutamate metabolism. Objectives: The purpose of the study was determination of genetic overlap between affective disorders using association analysis of M18 and M23 SNPs of DAOA/G72 gene with schizophrenia and bipolar disorder. Patients and Methods:In this case-control study, in order to evaluate the potential association of DAOA gene with schizophrenia and bipolar disorder in a southwest Iran population, two single nucleotide polymorphisms M18 and M23 were genotyped by the PCR-RFLP method and sequencing assay in 127 normal controls and 100 patients with schizophrenia and 100 patients with bipolar disorder. Data were analyzed by Logistic Regression and Mantel-Haenszel chi square tests. Results: Our finding showed that the M18 was significantly associated with bipolar disorder. We observed there is overlap association in M23 with schizophrenia and bipolar disorder. Also, our results indicated that the coexistence of the A and T alleles from the two polymorphisms, M18 and M23, increase the risk for schizophrenia and bipolar disorder. Conclusions: In summary, our data provides further evidence for a positive association between the DAOA locus and schizophrenia and bipolar disorder, these results may provide further support for genetic overlap in DAOA gene between schizophrenia and bipolar disorder.

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“…(3) The overall sample size included in the meta-analysis was relatively small (1658 patients and 2046 control subjects). 21 To overcome these limitations, a replication study using larger samples or samples of other populations will be required for conclusive results.…”

Section: Discussionmentioning

confidence: 99%

Serotonin 1A receptor gene and major depressive disorder: an association study and meta-analysis

et al. 2009

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Several genetic studies have shown an association between the 5-HT1A receptor gene (HTR1A) and major depressive disorder (MDD); however, results have been rather inconsistent. Moreover, to our knowledge, no association study on HTR1A and MDD in the Japanese population has been reported. Therefore, to evaluate the association between HTR1A and MDD, we conducted a case-control study of Japanese population samples with two single-nucleotide polymorphisms (SNPs), including rs6295 (C-1019G) in HTR1A. In addition, we conducted a meta-analysis of rs6295, which has been examined in other papers. Using one functional SNP (rs6295) and one tagging SNP (rs878567) selected with the HapMap database, we conducted a genetic association analysis of case-control samples (331 patients with MDD and 804 controls) in the Japanese population. Seven population-based association studies, including this study, met our criteria for the meta-analysis of rs6295. We found an association between rs878567 and Japanese MDD patients in the allele-wise analysis, but the significance of this association did not remain after Bonferroni's correction. We also did not detect any association between HTR1A and MDD in the allele/ genotype-wise or haplotype-wise analysis. On the other hand, we detected an association between rs6295 and MDD in the metaanalysis (P(Z)¼0.0327). In an explorative analysis, rs6295 was associated with Asian MDD patients after correction for multiple testing (P(Z)¼0.0176), but not with Caucasian MDD patients (P(Z)¼0.138). Our results suggest that HTR1A may not have a role in the pathophysiology of Japanese MDD patients. On the other hand, according to the meta-analysis, HTR1A was associated with MDD patients, especially in the Asian population. Keywords: case-control study; functional SNP; major depressive disorder (MDD); meta-analysis; serotonin 1A receptor gene (HTR1A); tagging SNP INTRODUCTION Altered serotonergic neural transmission is hypothesized to be a susceptibility factor for major depressive disorder (MDD). The evidence for such an association is discussed in more detail in reviews. 1,2 Several genetic studies have shown an association between the serotonin 1A (5-HT1A) receptor gene (HTR1A) and MDD; however, results have been rather inconsistent. A recent meta-analysis showed no association between HTR1A and MDD. 3 However, two very recent studies reported that rs6295 (C-1019G) in the promoter region of HTR1A, which regulates HTR1A transcription, 4,5 was associated with MDD in the Chinese population. 6,7 Moreover, to our knowledge, no association study of HTR1A and MDD in the Japanese population has been reported. Therefore, we examined the association between HTR1A and MDD in the Japanese, using the recently recommended strategy of 'genebased' association analysis. 8 Moreover, we conducted an updated

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Allelic association of G72/G30 with schizophrenia and bipolar disorder: A comprehensive meta-analysis

Cited by 92 publications

References 58 publications

d-Amino Acid Oxidase Activity Is Inhibited by an Interaction with Bassoon Protein at the Presynaptic Active Zone

d-Amino Acid Oxidase Activity Is Inhibited by an Interaction with Bassoon Protein at the Presynaptic Active Zone

Genetic Overlap Between Affective Disorders: An Association Analysis of M18 and M23 SNPs of DAOA/G72 Gene With Schizophrenia and Bipolar Disorder

Serotonin 1A receptor gene and major depressive disorder: an association study and meta-analysis

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