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Genetic vulnerability to DUSP22 promotor hypermethylation is involved in the relation between in utero famine exposure and schizophrenia

ABSTRACT: Genetic vulnerability to DUSP22 promotor hypermethylation is involved in the relation between in utero famine exposure and schizophrenia

PROVIDER: PRJNA478327 | ENA |

REPOSITORIES: ENA

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Genetic vulnerability to DUSP22 promotor hypermethylation is involved in the relation between in utero famine exposure and schizophrenia (DUTCHSCZ Data Set)

Project description:Epigenetic changes may account for the doubled risk to develop schizophrenia in individuals exposed to famine in utero. We therefore investigated DNA methylation in a unique sample of patients and healthy individuals conceived during the great famine in China. Subsequently we examined two case-control samples without famine exposure in whole blood and brain tissue. To shed light on the causality of the relation between famine exposure and DNA methylation we exposed human fibroblasts to nutritional deprivation. In the famine exposed schizophrenia patients we found significant hypermethylation of the dual specificity phosphatase 22 (DUSP22) gene promoter (Chr6:291687-293285) (N=153, p=0.01). In this sample DUSP22 methylation was also significantly higher in patients independent of famine exposure (p=0.025), suggesting that hypermethylation of DUSP22 is also more generally involved in schizophrenia risk. Similarly, DUSP22 methylation was also higher in two separate case-control sample not exposed to famine using DNA from whole blood (N=64, p=0.03) and postmortem brains (N=214, p=0.007). DUSP22 methylation showed strong genetic regulation across chromosomes by a region on chromosome 16 which was consistent with new 3D genome interaction data. The presence of a direct link between famine and DUSP22 transcription was supported by data from cultured human fibroblasts that showed increased methylation (p=0.048) and expression (p=0.019) in response to nutritional deprivation (N=10). These results highlight a first epigenetic locus that is genetically regulated across chromosomes and that is involved in the response to early life exposure to famine and that is relevant for a major psychiatric disorder.

2018-06-29 | GSE116378 | GEO

Genetic vulnerability to DUSP22 promotor hypermethylation is involved in the relation between in utero famine exposure and schizophrenia (CHINFAM Data Set)

2018-06-29 | GSE116379 | GEO

Genetic vulnerability to DUSP22 promotor hypermethylation is involved in the relation between in utero famine exposure and schizophrenia (DUTCHSCZ Data Set)

Project description:Genetic vulnerability to DUSP22 promotor hypermethylation is involved in the relation between in utero famine exposure and schizophrenia (DUTCHSCZ Data Set)

| PRJNA478330 | ENA

Genetic vulnerability to DUSP22 promotor hypermethylation is involved in the relation between in utero famine exposure and schizophrenia (CHINFAM Data Set)

Project description:Genetic vulnerability to DUSP22 promotor hypermethylation is involved in the relation between in utero famine exposure and schizophrenia (CHINFAM Data Set)

| PRJNA478331 | ENA

Genetic vulnerability to DUSP22 promotor hypermethylation is involved in the relation between in utero famine exposure and schizophrenia

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-06-29 | GSE116380 | GEO

Genetic vulnerability to DUSP22 promoter hypermethylation is involved in the relation between in utero famine exposure and schizophrenia.

Project description:Epigenetic changes may account for the doubled risk to develop schizophrenia in individuals exposed to famine in utero. We therefore investigated DNA methylation in a unique sample of patients and healthy individuals conceived during the great famine in China. Subsequently, we examined two case-control samples without famine exposure in whole blood and brain tissue. To shed light on the causality of the relation between famine exposure and DNA methylation, we exposed human fibroblasts to nutritional deprivation. In the famine-exposed schizophrenia patients, we found significant hypermethylation of the dual specificity phosphatase 22 (DUSP22) gene promoter (Chr6:291687-293285) (N = 153, p = 0.01). In this sample, DUSP22 methylation was also significantly higher in patients independent of famine exposure (p = 0.025), suggesting that hypermethylation of DUSP22 is also more generally involved in schizophrenia risk. Similarly, DUSP22 methylation was also higher in two separate case-control samples not exposed to famine using DNA from whole blood (N = 64, p = 0.03) and postmortem brains (N = 214, p = 0.007). DUSP22 methylation showed strong genetic regulation across chromosomes by a region on chromosome 16 which was consistent with new 3D genome interaction data. The presence of a direct link between famine and DUSP22 transcription was supported by data from cultured human fibroblasts that showed increased methylation (p = 0.048) and expression (p = 0.019) in response to nutritional deprivation (N = 10). These results highlight an epigenetic locus that is genetically regulated across chromosomes and that is involved in the response to early-life exposure to famine and that is relevant for a major psychiatric disorder.

| S-EPMC6104043 | biostudies-literature

Identification of active promotor regions in Wilms tumor cells

Project description:The goal of this study was to find differences in the chromatin state (active promotor regions) between two Wilms tumor subtypes (blastemal and non-blastemal).

2020-05-09 | GSE98721 | GEO

Relief Food Subsistence Revealed by Microparticle and Proteomics Analyses of Dental Calculus From Victims of the Great Irish Famine

Project description:Food and diet were class markers in nineteenth-century Ireland, which became evident as nearly one million people, primarily the poor and destitute, died as a consequence of the notorious Great Famine of 1845–1852. Famine took hold after a blight (Phytophthora infestans) destroyed the only means of subsistence—the potato crop—for a significant proportion of the population. This study seeks to elucidate the variability of diet in mid-nineteenth-century Ireland through microparticle and proteomic analysis of human dental calculus samples (n = 42) from victims of the Famine. The sample derives from remains of people who died between August 1847 and March 1851 while receiving poor relief as inmates in the union workhouse in the city of Kilkenny (52°39’N, -7°15’W). The results corroborate the historical accounts of food provisions before and during the Famine, with evidence of corn (maize), potato and cereal starch granules from the microparticle analysis and milk proteins from the proteomic analysis. Unexpectedly, there is also evidence of egg proteins—a food source generally reserved only for export and the better-off social classes—which highlights the variability of the Famine experience for those who died. Through historical contextualisation, this study shows how the notoriously monotonous potato diet of the nineteenth-century Irish poor was supplemented by other foodstuffs on an opportunistic basis. While the Great Irish Famine was one of the worst subsistence crises in history, it was foremost a social disaster induced by the lack of access to food and not the lack of food availability.

2019-10-17 | PXD015002 | Pride

Regulation of YAP Promotor Accessibility in Endothelial Mechanotransduction

Project description:Regulation of YAP Promotor Accessibility in Endothelial Mechanotransduction

| PRJNA1066889 | ENA

Proteomic investigation of a mixed microbial culture synthesizing polyhydroxyalkanoates from fermented dairy manure under aerobic feast-famine conditions

Project description:Polyhydroxyalkanoates (PHAs) are bio-based, biodegradable polyesters that can be produced from organic-rich waste streams using mixed microbial cultures. To maximize PHA production, mixed microbial cultures may be enriched for PHA-producing bacteria with a high storage capacity through the imposition of cyclic, aerobic feast-famine conditions in a sequencing batch reactor (SBR). Though enrichment SBRs have been extensively investigated a bulk solutions-level, little evidence at the proteome level is available to describe the observed SBR behavior to guide future SBR optimization strategies. As such, the purpose of this investigation was to characterize proteome dynamics of a mixed microbial culture in an SBR operated under aerobic feast-famine conditions using fermented dairy manure as the feedstock for PHA production. At the beginning of the SBR cycle, excess PHA precursors were provided to the mixed microbial culture (i.e., feast), after which followed a long duration devoid of exogenous substrate (i.e., famine). Two-dimensional electrophoresis was used to separate protein mixtures during a complete SBR cycle, and proteins of interest were identified.

2017-01-31 | PXD003126 | Pride

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