Association of schizophrenia with DTNBP1 but not with DAO, DAOA, NRG1 and RGS4 nor their genetic interaction

Vilella, Elisabet; Costas, Javier; Sanjuán, Julio; Guitart, Míriam; Diego, Yolanda de; Carracedo, Ángel; Martorell, Lourdes; Valero, Joaquı́n; Labad, Antonio; Frutos, Rosa de; Nájera, Carmén; Moltó, María Dolores; Toirac, I.; Guillamat, Roser; Brunet, Anna; Vallès, Vicenç; Pérez, Lucía; Leon, Melquíades; Fonseca, Fernando Rodrı́guez de; Phillips, C.; Torres, M.

doi:10.1016/j.jpsychires.2007.02.005

Cited by 80 publications

(49 citation statements)

References 68 publications

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“…[261][262][263] However, some studies have failed to find an association between mutations in NRG1 and schizophrenia. 264,265 A recent meta-analysis of 13 human association studies of NRG1 found that 6 polymorphisms in NRG1, as well as at-risk haplotypes, showed a strong and consistent positive association with schizophrenia. 266 Another recent meta-analysis also found several polymorphisms of NRG1 that were significantly associated with the development of schizophrenia.…”

Section: Neuregulin-1 (Nrg1)mentioning

confidence: 99%

Contribution of nonprimate animal models in understanding the etiology of schizophrenia

Lazar

Neufeld²,

Cain³

2011

jpn

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Section: Neuregulin-1 (Nrg1)mentioning

confidence: 99%

Contribution of nonprimate animal models in understanding the etiology of schizophrenia

Lazar

Neufeld²,

Cain³

2011

jpn

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“…An association has been reported in multiple independent studies (Addington et al, 2004;Chen et al, 2004;Fallin et al, 2005;Hall et al, 2004;Hong et al, 2006;Korostishevsky et al, 2004;Korostishevsky et al, 2006;Ma et al, 2006;Schulze et al, 2005;Schumacher et al, 2004;Wang et al, 2004;Williams et al, 2006;Yue et al, 2006;Yue et al, 2007;Zou et al, 2005). However, several studies did not find association with traditional BP or SCZ phenotype (Bakker et al, 2007;Goldberg et al, 2006;Liu et al, 2006;Mulle et al, 2005;Vilella et al, 2007;Wood et al, 2006). In addition, an obvious inconsistency of allelic association(s) has been observed.…”

Section: Introductionmentioning

confidence: 99%

“…Since then, 13 more G72/G30 association studies in SCZ and three more in BP have been published (Bakker et al, 2007;Fallin et al, 2005;Goldberg et al, 2006;Hong et al, 2006;Korostishevsky et al, 2006;Liu et al, 2006;Ma et al, 2006;Nicodemus et al, 2007;Schulze et al, 2005;Vilella et al, 2007;Williams et al, 2006;Wood et al, 2006;Yue et al, 2006;Yue et al, 2007), with inconsistent associated alleles or haplotypes. Here we report an updated meta-analysis to re-evaluate the relationship between variants in the G72/G30 gene region and these two major psychiatric disorders.…”

Section: Introductionmentioning

confidence: 99%

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

Shi

Badner

Gershon

et al. 2008

Schizophrenia Research

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The G72/G30 gene complex (G72 also known as D-amino acid oxidase activator, DAOA) and its chromosomal region 13q32-34 have been linked and associated with both schizophrenia (SCZ) and bipolar disorder (BP) in multiple studies, including our initial association report on BP. However, the inconsistency of associated variants across studies is obvious. Previous meta-analyses had small data sets. The present meta-analysis combined 18 association articles published before April of 2007. There were 19 independent studies of SCZ, with 4304 cases, 5423 controls, and 1384 families, and four independent studies of BP with 1145 cases, 1829 controls, and 174 families. Of 15 single nucleotide polymorphisms (SNPs) analyzed in the 95-kb G72/G30 gene region, M18/rs947267 and M22/rs778293 showed association with SCZ in Asians, and M24/rs1421292 with SCZ in Europeans. The associations of C allele at M18 and A allele at M22 with SCZ in Asians survived conservative Bonferroni correction for multiple testing for 15 markers and subgroup analysis (adjusted P = 0.0000253 for M18; adjusted P = 0.009 for M22). No single maker showed evidence of overall association with BP. These results suggest that G72/G30 may influence susceptibility to schizophrenia with weak effects.

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“…DTNBP1 encodes the protein dystrobrevin-binding protein 1 (dysbindin-1) (26)(27)(28). More broadly, reduction in dysbindin-1 expression has been found in the schizophrenia population (16,27,29), indicating that reduced dysbindin-1 protein levels may be a common disease trait of schizophrenia.…”

mentioning

confidence: 99%

Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final common disease mechanism in schizophrenia

Carlson

Talbot²,

Halene³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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DTNBP1 (dystrobrevin binding protein 1) is a leading candidate susceptibility gene in schizophrenia and is associated with working memory capacity in normal subjects. In schizophrenia, the encoded protein dystrobrevin-binding protein 1 (dysbindin-1) is often reduced in excitatory cortical limbic synapses. We found that reduced dysbindin-1 in mice yielded deficits in auditory-evoked response adaptation, prepulse inhibition of startle, and evoked γ-activity, similar to patterns in schizophrenia. In contrast to the role of dysbindin-1 in glutamatergic transmission, γ-band abnormalities in schizophrenia are most often attributed to disrupted inhibition and reductions in parvalbumin-positive interneuron (PV cell) activity. To determine the mechanism underlying electrophysiological deficits related to reduced dysbindin-1 and the potential role of PV cells, we examined PV cell immunoreactivity and measured changes in net circuit activity using voltage-sensitive dye imaging. The dominant circuit impact of reduced dysbindin-1 was impaired inhibition, and PV cell immunoreactivity was reduced. Thus, this model provides a link between a validated candidate gene and an auditory endophenotypes. Furthermore, these data implicate reduced fast-phasic inhibition as a common underlying mechanism of schizophrenia-associated intermediate phenotypes.GABAergic | γ-oscillation | hippocampus | evoked response spectral perturbation | Sandy mouse P atients with schizophrenia have reduced amplitude and gating of auditory event-related potentials (ERPs) (1, 2). Recent clinical studies also show abnormal γ-band oscillations (30-100 Hz) as an endophenotype of the illness that is associated with reduced cognitive function (3-7). Work in animal models shows a prominent role of cortical inhibitory networks in generating γ-oscillations (8, 9), which in turn, supports the role of aberrant GABAergic inhibition as an important potential component of schizophrenia (4,7,10,11). The GABA-producing enzyme glutamic acid decarboxylase is dysregulated in schizophrenia, and postsynaptic GABA A receptors are dysregulated as well (4). Risk alleles for GABA A receptor subunits are also associated with the disease (12, 13), although linkage is weaker than the linkage found with dysbindin-1 and other candidate genes such as DISC1 (14). At the anatomical level, there is a loss of immunoreactivity for parvalbumin (PV) in schizophrenia. PV is a calcium-binding protein marker for a class of fast-spiking GABAergic neurons. It is debated whether reduced PV in postmortem studies is caused by reduction in cell number or merely loss of protein expression. In either case, reduced PV immunoreactivity suggests disruption of an important source of local circuit inhibition (4, 15).Although clinical electrophysiological and postmortem anatomical findings support the role of GABA dysfunction in schizophrenia, a larger set of schizophrenia risk haplotypes are thought to confer reduced NMDA receptor-mediated function and changes in glutamatergic transmission [e.g., DISC1; Neuregu...

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Association of schizophrenia with DTNBP1 but not with DAO, DAOA, NRG1 and RGS4 nor their genetic interaction

Cited by 80 publications

References 68 publications

Contribution of nonprimate animal models in understanding the etiology of schizophrenia

Contribution of nonprimate animal models in understanding the etiology of schizophrenia

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

Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final common disease mechanism in schizophrenia

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