Association analyses of the <i>neuregulin 1</i> gene with schizophrenia and manic psychosis in a Hispanic population

Walss‐Bass, Consuelo; Raventós, Henriette; Montero, Ana Patricia; Armas, Regina; Dassori, Albana M; Contreras, Salvador; Liu, W.; Medina, Rolando; Levinson, Douglas F.; Pereira, Mariana; Leach, Robin J.; Almasy, Laura; Escamilla, Michael

doi:10.1111/j.1600-0447.2005.00631.x

Cited by 41 publications

(22 citation statements)

References 37 publications

(42 reference statements)

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“…10) (52). Moreover, the cleavage site is exactly at the peptide bond Cys-321/Val-322, just one amino acid N-terminal to the schizophrenia-associated V322L mutation (28). Consistent with previous findings, this mutation affects the turnover of the CTF (29), which may even be responsible for schizophrenia-like phenotypes in BACE1 Ϫ/Ϫ mice (30).…”

Section: Discussionsupporting

confidence: 75%

“…Whereas most disease-associated SNPs are located in non-coding regions of the NRG1 gene, one SNP causes a valine to leucine exchange at amino acid 322 in the C-terminal TMD of NRG1 (28). Interestingly, this mutation is located immediately C-terminal of the ⑀-like cleavage site identified in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, a schizophrenia-associated single nucleotide polymorphism (SNP; valine to leucine) close to the C-terminal end of the NRG1 type III TMD (Fig. 1A) (28) appears to result in an accumulation of the type 1-oriented CTF (29), suggesting that ␥-secretase cleavage is disturbed. Consistent with that finding, BACE1 knock-out mice exhibit schizophrenia-like behavioral phenotypes (30).…”

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confidence: 99%

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Proteolytic Processing of Neuregulin 1 Type III by Three Intramembrane-cleaving Proteases

Fleck¹,

Voß²,

Brankatschk

et al. 2016

Journal of Biological Chemistry

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Numerous membrane-bound proteins undergo regulated intramembrane proteolysis. Regulated intramembrane proteolysis is initiated by shedding, and the remaining stubs are further processed by intramembrane-cleaving proteases (I-CLiPs). Neuregulin 1 type III (NRG1 type III) is a major physiological substrate of ␤-secretase (␤-site amyloid precursor proteincleaving enzyme 1 (BACE1)). BACE1-mediated cleavage is required to allow signaling of NRG1 type III. Because of the hairpin nature of NRG1 type III, two membrane-bound stubs with a type 1 and a type 2 orientation are generated by proteolytic processing. We demonstrate that these stubs are substrates for three I-CLiPs

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Section: Discussionsupporting

confidence: 75%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Proteolytic Processing of Neuregulin 1 Type III by Three Intramembrane-cleaving Proteases

Fleck¹,

Voß²,

Brankatschk

et al. 2016

Journal of Biological Chemistry

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“…4 However, the current evidence of overlap of genetic susceptibility for SC and BP has led to the question of whether the understanding of a common pathophysiology of psychotic-related disorders will lead to a change in the way we classify these disorders. [5][6][7] We have previously used psychosis as a phenotype for association studies of different regions of the genome [8][9][10] using subjects from the Central Valley of Costa Rica (CVCR). We have found in this population evidence of association of psychosis with three loci on chromosome 18.…”

Section: Introductionmentioning

confidence: 99%

TGFB-induced factor (TGIF): a candidate gene for psychosis on chromosome 18p

et al. 2007

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Schizophrenia (SC) and bipolar disorder (BP) share many clinical features, among them psychosis. We previously identified a putative gene locus for psychosis on chromosome 18p in a sample from the Central Valley of Costa Rica (CVCR) population. The present study replicated the association to a specific allele of microsatellite marker D18S63 on 18p11.3, using a newly collected sample from the CVCR. A combined analysis of both samples, plus additional subjects, showed that this specific allele on D18S63, which lies within an intron on the TGFB-induced factor (TGIF ) gene, is strongly associated (P-value = 0.0005) with psychosis. Eleven additional SNP markers, spanning five genes in the region, were analyzed in the combined sample from the CVCR. Only the four SNPs within the TGIF gene were in strong linkage disequilibrium with D18S63 (D 0 = 1.00). A specific haplotype for all five markers within the TGIF gene showed evidence of association (P-value = 0.011) to psychosis. A second, distinct haplotype, containing a newly identified nonsynonymous polymorphism in exon 5 of the TGIF gene, showed a nonsignificant trend towards association to psychosis (P-value = 0.077). TGIF is involved in neurodevelopment, neuron survival and controls the expression of dopamine receptors. Altogether, our results point to the possible involvement of TGIF in the pathophysiology of psychotic disorders in the CVCR population.

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“…This candidate gene approach usually ). In addition, as genes have been discovered for schizophrenia, investigators have also analyzed whether these genes might be associated with bipolar disorder, with several studies now suggesting that variations in the Neuregulin 1 gene 96,97 and the G72/30 gene 98,99 are associated with bipolar disorder or manic psychosis. Replication of genetic association studies has been difficult, in part because the sample sizes necessary to detect genes are of small effect size.…”

Section: Candidate Genesmentioning

confidence: 99%

3. Genetics of Bipolar Disorder

Bengesser¹,

Reininghaus²

Genetics of Bipolar Disorder

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ipolar affective disorder, type I (BP-I) is a severe mental illness marked by periodic extremes of mood state (manias), as well as (in most cases) episodes of depression and (in many cases) psychosis. The consequences of BP-I are severe, and involve both direct and indirect issues. Rates of suicide in BP-I patients are high, 1,2 and BP-I subjects also suffer from poorer quality of life and lower productivity than unaffected individuals.3 Annual public health costs (combined direct and indirect) of BP have been estimated to be between 24 billion and 45 billion dollars.4,5 BP-I occurs in all populations that have been studied, with lifetime prevalence rates worldwide of the order of one per every 100 individuals. 6 Segregation analyses, adoption studies, and twin studies have consistently shown that, regardless of the population studied, genetic factors play an important role in determining one's risk of developing BP-I. [7][8][9] Since little is known about the actual etiology of BP, it would be a major contribution to our understanding of the pathophysiology of BP if the genes responsible for the neurobiologic changes which underlie this disorder could be identified. The difficulty in finding genetic loci that are involved in BP most likely derives from the complex nature of the illness. When multiple transmission models for BP-I (the most severe form of BP) have been tested, oligogenic epistatic models are found to be the best fit, rather than models which purport one major locus. Craddock et al 10 reviewed epidemiologic, family, and twin studies, and showed that two, three, or four locus models 141T r a n s l a t i o n a l r e s e a r c h B

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Association analyses of the neuregulin 1 gene with schizophrenia and manic psychosis in a Hispanic population

Abstract: These results suggest that the neuregulin 1 gene is unlikely to play a major role in predisposing to schizophrenia in the CVCR. Further studies in the CVCR and other Latin American populations should be performed in order to corroborate these findings.

Cited by 41 publications

References 37 publications

Proteolytic Processing of Neuregulin 1 Type III by Three Intramembrane-cleaving Proteases

Proteolytic Processing of Neuregulin 1 Type III by Three Intramembrane-cleaving Proteases

TGFB-induced factor (TGIF): a candidate gene for psychosis on chromosome 18p

3. Genetics of Bipolar Disorder

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