Effect of metabotropic glutamate receptor-3 variants on prefrontal brain activity in schizophrenia: An imaging genetics study using multi-channel near-infrared spectroscopy

Kinoshita, Akihide; Takizawa, Ryu; Koike, Shinsuke; Satomura, Yoshihiro; Kawasaki, Shingo; Kawakubo, Yuki; Marumo, Kohei; Tochigi, Mamoru; Sasaki, Tsukasa; Nishimura, Yukika; Kasai, Kiyoto

doi:10.1016/j.pnpbp.2015.04.006

Cited by 11 publications

(9 citation statements)

References 59 publications

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“… 1 Among these associations, the metabotropic glutamate receptor 3 ( GRM3 ) contained the second most significant single-nucleotide polymorphism (SNP) (rs12704290, P =3.33 × 10 −10 ). 1 This PGC finding complements a number of previous associations between GRM3 and schizophrenia-related phenotypes, such as prefrontal activation during cognitive tasks, 2 white matter integrity, 3 hippocampal volume in severe obstetric complications, 4 poor cognitive performance (that is, verbal fluency, digit symbol test, perseverative error processing and spatial working memory), 5 , 6 , 7 , 8 , 9 antipsychotic response in first-episode schizophrenia 10 and positive symptoms severity in treatment-resistant schizophrenia. 5 However, two meta-analyses of GRM3 SNPs have failed to support an association with schizophrenia risk.…”

Section: Introductionsupporting

confidence: 76%

“…Since the publication of the most recent GRM3 meta-analysis, 12 there have been three additional studies published involving 6027 (2381 schizophrenia and 3646 control) individuals, 2 , 6 , 13 indicating a reappraisal is warranted. Thus, the aim of this study was to provide an updated and more comprehensive meta-analysis of the association between GRM3 genetic variation and schizophrenia by including both case–control and family studies as well as an exploration of potential population stratification.…”

Section: Introductionmentioning

confidence: 99%

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Meta-analysis supports GWAS-implicated link between GRM3 and schizophrenia risk

et al. 2017

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Genome-wide association study (GWAS) evidence has identified the metabotropic glutamate receptor 3 (GRM3) gene as a potential harbor for schizophrenia risk variants. However, previous meta-analyses have refuted the association between GRM3 single-nucleotide polymorphisms (SNPs) and schizophrenia risk. To reconcile these conflicting findings, we conducted the largest and most comprehensive meta-analysis of 14 SNPs in GRM3 from a total of 11 318 schizophrenia cases, 13 820 controls and 486 parent–proband trios. We found significant associations for three SNPs (rs2237562: odds ratio (OR)=1.06, 95% confidence interval (CI)=1.02–1.11, P=0.017; rs13242038: OR=0.90, 95% CI=0.85–0.96, P=0.016 and rs917071: OR=0.94, 95% CI=0.91–0.97, P=0.003). Two of these SNPs (rs2237562, rs917071) were in strong-to-moderate linkage disequilibrium with the top GRM3 GWAS significant SNP (rs12704290) reported by the Schizophrenia Working Group of the Psychiatric Genomics Consortium. We also found evidence for population stratification related to rs2237562 in that the ‘risk’ allele was dependent on the population under study. Our findings support the GWAS-implicated link between GRM3 genetic variation and schizophrenia risk as well as the notion that alleles conferring this risk may be population specific.

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Section: Introductionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Meta-analysis supports GWAS-implicated link between GRM3 and schizophrenia risk

et al. 2017

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“…1,2 Although initial trials with mGluR2/3 agonists have had mixed results, [3][4][5][6][7] data increasingly indicate that changes in mGluR3 are associated with schizophrenia and aging, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] encouraging this treatment strategy. Clinical trials were originally based on data from rodent models.…”

Section: Introductionmentioning

confidence: 99%

“…45,46 Insults to disrupted in schizophrenia 1 and phosphodiesterase 4A are linked to increased risk of illness. 47,48 Importantly, genetic alterations in mGluR3 are increasingly linked to schizophrenia, [8][9][10][11][12][13][14][15][16][17][18][19][20][21] including altered dlPFC activation and poorer cognitive performance. 9,11 In particular, there is reduced mGluR3 protein in schizophrenia dlPFC, and an increase in GCPII, the enzyme that catabolizes the endogenous mGluR3 ligand, NAAG.…”

Section: Introductionmentioning

confidence: 99%

mGluR2/3 mechanisms in primate dorsolateral prefrontal cortex: evidence for both presynaptic and postsynaptic actions

et al. 2017

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“…In particular, the authors reported one SNP, located in an intronic region of the gene, to be significantly associated with white matter integrity. Recently a study on a Japanese cohort composed by 21 patients and 48 control analyzed 4 GRM3 SNP and found one of them to be associated with prefrontal brain activity though only in the SCZ group [ 41 ].…”

Section: Insights From Candidate Gene Approach Studiesmentioning

confidence: 99%

The Role of Metabotropic Glutamate Receptor Genes in Schizophrenia

Maj

Minelli

Giacopuzzi

et al. 2016

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Genomic studies revealed two main components in the genetic architecture of schizophrenia, one constituted by common variants determining a distributed polygenic effect and one represented by a large number of heterogeneous rare and highly disruptive mutations. These gene modifications often affect neural transmission and different studies proved an involvement of metabotropic glutamate receptors in schizophrenia phenotype. Through the combination of literature information with genomic data from public repositories, we analyzed the current knowledge on the involvement of genetic variations of the human metabotropic glutamate receptors in schizophrenia and related endophenotypes. Despite the analysis did not reveal a definitive connection, different suggestive associations have been identified and in particular a relevant role has emerged for GRM3 in affecting specific schizophrenia endophenotypes. This supports the hypothesis that these receptors are directly involved in schizophrenia disorder.

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Effect of metabotropic glutamate receptor-3 variants on prefrontal brain activity in schizophrenia: An imaging genetics study using multi-channel near-infrared spectroscopy

Cited by 11 publications

References 59 publications

Meta-analysis supports GWAS-implicated link between GRM3 and schizophrenia risk

Meta-analysis supports GWAS-implicated link between GRM3 and schizophrenia risk

mGluR2/3 mechanisms in primate dorsolateral prefrontal cortex: evidence for both presynaptic and postsynaptic actions

The Role of Metabotropic Glutamate Receptor Genes in Schizophrenia

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