Neuregulin 1 (NRG1) and schizophrenia: analysis of a US family sample and the evidence in the balance

Duan, Jubao; Martínez, María; Sanders, Alan R.; Hou, Cuiping; Krasner, Aaron; Schwartz, D.; Gejman, Pablo V.

doi:10.1017/s0033291705005428

Cited by 43 publications

(27 citation statements)

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“…53 On 8p21-p12 lies the second of the two most strongly implicated susceptibility genes, neuregulin1 (NRG1), 45 although other reports could not replicate this finding. 54 NRG1 is associated with synaptic remodeling, neuronal migration and brain development and appears to influence glutamatergic function through regulation of NMDA receptors. 55,56 Further, NRG1 has been studied to have a key role in neurodevelopmental process in central nervous system (CNS) that includes oligodendrocyte development.…”

Section: Chromosomes 6 Andmentioning

confidence: 99%

The myelin-pathogenesis puzzle in schizophrenia: a literature review

2007

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Schizophrenia is a serious and disabling mental disorder with symptoms such as auditory hallucinations, disordered thinking and delusions, avolition, anhedonia, blunted affect and apathy. In this review article we seek to present the current scientific findings from linkage studies and susceptible genes and the pathophysiology of white matter in schizophrenia. The article has been reviewed in two parts. The first part deals with the linkage studies and susceptible genes in schizophrenia in order to have a clear-cut picture of the involvement of chromosomes and their genes in schizophrenia. The genetic linkage results seem to be replicated in some cases but in others are not. From these results, we cannot draw a fine map to a single locus or gene, leading to the conclusion that schizophrenia is not caused by a single factor/gene. In the second part of the article we present the oligodendrocyte-related genes that are associated with schizophrenia, as we hypothesize a potential role of oligodendrocyte-related genes in the pathology of the disorder.

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Section: Chromosomes 6 Andmentioning

confidence: 99%

The myelin-pathogenesis puzzle in schizophrenia: a literature review

2007

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“…As estimated by TDT-PC (transmission disequilibrium testpower calculator) software [40] , our sample has about 87% power to detect a locus with a relative risk (RR) of 2 at a significance level of 5%; but power drops to 44% for an RR of 1.4 [41] . [8] .…”

Section: Subjects and Phenotypingmentioning

confidence: 99%

DTNBP1 (Dystrobrevin Binding Protein 1) and Schizophrenia: Association Evidence in the 3′ End of the Gene

et al. 2007

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Objectives:Dysbindin (DTNBP1) has been identified as a susceptibility gene for schizophrenia (SZ) through a positional approach. However, a variety of single nucleotide polymorphisms (SNPs) and haplotypes, in different parts of the gene, have been reported to be associated in different samples, and a precise molecular mechanism of disease remains to be defined. We have performed an association study with two well-characterized family samples not previously investigated at the DTNBP1 locus. Methods: We examined 646 subjects in 136 families with SZ, largely of European ancestry (EA), genotyping 26 SNPs in DTNBP1. Results: Three correlated markers (rs875462, rs760666, and rs7758659) at the 3′ region of DTNBP1 showed evidence for association to SZ (p = 0.004), observed in both the EA (p = 0.031) and the African American (AA) subset (p = 0.045) with the same over-transmitted allele. The most significant haplotype in our study was rs7758659-rs3213207 (global p = 0.0015), with rs3213207 being the most frequently reported associated marker in previous studies. A non-conservative missense variant (Pro272Ser) in the 3′ region of DTNBP1 that may impair DTNBP1 function was more common in SZ probands (8.2%) than in founders (5%) and in dbSNP (2.1%), but did not reach statistical significance. Conclusion: Our results provide evidence for an association of SZ with SNPs at the 3′ end of DTNBP1 in the samples studied.

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“…Chromosome 8p has been suggested repeatedly as a linkage region for both SZ and BPD; however, the underlying genes responsible for the linkage signal remain elusive. NRG1 was identified as one candidate gene from this region and was associated with SZ (Stefansson et al, 2002(Stefansson et al, , 2003Williams et al, 2003;Yang et al, 2003;Corvin et al, 2004;Li et al, 2004;Tang et al, 2004;Petryshen et al, 2005) and BPD (Green et al, 2005) in some studies but could not be confirmed by others (Bakker et al, 2004;Hong et al, 2004;Iwata et al, 2004;Thiselton et al, 2004;Duan et al, 2005;Liu et al, 2005). This inconsistency might be due to several factors including clinical heterogeneity, population stratification, different haplotype structure between populations, and limited statistical power.…”

Section: Vmat1 and Bipolar Disordermentioning

confidence: 99%

“…Recent linkage studies have suggested that a susceptibility locus for BPD exists on chromosome 8p21-22 (Cichon et al, 2001;Ophoff et al, 2002;Park et al, 2004;Cheng et al, 2006). Interestingly, numerous linkage studies in schizophrenia (SZ) report a susceptibility locus on 8p21 (Pulver et al, 1995(Pulver et al, , 2000Kendler et al, 1996;Straub et al, 1996;Blouin et al, 1998;Brzustowicz et al, 1999;Gurling et al, 2001;Stefansson et al, 2002;Lewis et al, 2003;Suarez et al, 2006) and a candidate gene from this region, neuregulin 1 (NRG1), was associated with SZ (Stefansson et al, 2002(Stefansson et al, , 2003Williams et al, 2003;Yang et al, 2003;Corvin et al, 2004;Li et al, 2004;Tang et al, 2004;Petryshen et al, 2005); however, NRG1 is located about 10-15 cM away from the major linkage peaks and others could not confirm an association between the NRG1 gene and SZ (Bakker et al, 2004;Hong et al, 2004;Iwata et al, 2004;Thiselton et al, 2004;Duan et al, 2005;Liu et al, 2005). The report of multiple linkage studies in BPD and SZ supports the hypothesis of a shared susceptibility locus for BPD and SZ on 8p (Berrettini, 2003(Berrettini, , 2004.…”

Section: Introductionmentioning

confidence: 99%

Variations in the Vesicular Monoamine Transporter 1 Gene (VMAT1/SLC18A1) are Associated with Bipolar I Disorder

Lohoff

Dahl

Ferraro

et al. 2006

Neuropsychopharmacol

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The vesicular monoamine transporter 1 gene (VMAT1/SLC18A1) maps to the shared bipolar disorder (BPD)/schizophrenia (SZ) susceptibility locus on chromosome 8p21. Vesicular monoamine transporters are involved in transport of monoamine neurotransmitters which have been postulated to play a relevant role in the etiology of BPD and/or SZ. Variations in the VMAT1 gene might affect transporter function and/or expression and might be involved in the etiology of BPD and/or SZ. Genotypes of 585 patients with BPD type I and 563 control subjects were obtained for three missense single nucleotide polymorphisms (SNPs) (Thr4Pro, Thr98Ser, Thr136Ile) and four non-coding SNPs (rs988713, rs2279709, rs3735835, rs1497020). All cases and controls were of European descent. Allele frequencies differed significantly for the potential functional polymorphism Thr136Ser between BPD patients and controls (p ¼ 0.003; df ¼ 1; OR ¼ 1.34; 95% CI: 1.11-1.62). Polymorphisms in the promoter region (rs988713: p ¼ 0.005, df ¼ 1; OR ¼ 1.31; 95% CI: 1.09-1.59) and intron 8 (rs2279709: p ¼ 0.039, df ¼ 1; OR ¼ 0.84; 95% CI: 0.71-0.99) were also associated with disease. Expression analysis confirmed that VMAT1 is expressed in human brain at the mRNA and protein level. Results suggest that variations in the VMAT1 gene may confer susceptibility to BPD in patients of European descent. Additional studies are necessary to confirm this effect and to elucidate the role of VMAT1 in central nervous system physiology.

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Neuregulin 1 (NRG1) and schizophrenia: analysis of a US family sample and the evidence in the balance

Cited by 43 publications

References 0 publications

The myelin-pathogenesis puzzle in schizophrenia: a literature review

The myelin-pathogenesis puzzle in schizophrenia: a literature review

<i>DTNBP1 (Dystrobrevin Binding Protein 1)</i> and Schizophrenia: Association Evidence in the 3′ End of the Gene

Variations in the Vesicular Monoamine Transporter 1 Gene (VMAT1/SLC18A1) are Associated with Bipolar I Disorder

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