Genetic vulnerability to DUSP22 promotor hypermethylation is involved in the relation between in utero famine exposure and schizophrenia (CHINFAM Data Set)
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ABSTRACT:
PROVIDER: PRJNA478331 | ENA |
REPOSITORIES: ENA
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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 | GSE116379 | GEO
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
Project description:Genetic vulnerability to DUSP22 promotor hypermethylation is involved in the relation between in utero famine exposure and schizophrenia
| PRJNA478327 | ENA
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
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-06-29 | GSE116380 | GEO
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
Project description:Skeletal muscle wasting results from numerous conditions, such as sarcopenia, glucocorticoid therapy or intensive care. It prevents independent living in the elderly, predisposes to secondary diseases, and ultimately reduces lifespan. There is no approved drug therapy and the major causative mechanisms are not fully understood. Dual specificity phosphatase 22 (DUSP22) is a pleiotropic signaling molecule that plays important roles in immunity and cancer. However, the role of DUSP22 in skeletal muscle wasting is unknown. In this study, DUSP22 was found to be upregulated in sarcopenia patients and models of skeletal muscle wasting. DUSP22 knockdown or pharmacological inhibition with BML-260 prevented multiple forms of muscle wasting. Mechanistically, targeting DUSP22 suppressed FOXO3a, a master regulator of skeletal muscle wasting, via downregulation of the stress-activated kinase JNK, which occurred independently of aberrant Akt activation. DUSP22 targeting was also effective in human skeletal muscle cells undergoing atrophy. In conclusion, phosphatase DUSP22 is a novel target for preventing skeletal muscle wasting and BML-260 is a therapeutically effective small molecule inhibitor. The DUSP22-JNK-FOXO3a axis could be exploited to treat sarcopenia or related aging disorders.
2025-03-25 | GSE292258 | GEO
Project description:Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas broadly segregated into ALK-positive and ALK-negative types. While ALK-positive ALCLs consistently bear rearrangements of the ALK tyrosine kinase gene, ALK-negative ALCLs are clinically and genetically heterogeneous. About 30% of ALK-negative ALCLs have rearrangements of DUSP22 and have excellent long-term outcomes with standard therapy. To better understand this group of tumors, we evaluated their molecular signature using gene expression profiling. DUSP22-rearranged ALCLs belonged to a distinct subset of ALCLs that lacked expression of genes associated with JAK-STAT3 signaling, a pathway contributing to growth in the majority of ALCLs. Reverse-phase protein array and immunohistochemical studies confirmed the lack of activated STAT3 in DUSP22-rearranged ALCLs. DUSP22-rearranged ALCLs also overexpressed immunogenic cancer-testis antigen (CTA) genes and showed marked DNA hypomethylation by reduced representation bisulfate sequencing and DNA methylation arrays. Pharmacologic DNA demethylation in ALCL cells recapitulated the overexpression of CTAs and other DUSP22 signature genes. Additionally, DUSP22-rearranged ALCLs minimally expressed PD-L1 compared to other ALCLs, but showed high expression of the costimulatory gene CD58 and HLA class II. Taken together, these findings indicate that DUSP22 rearrangements define a molecularly distinct subgroup of ALCLs and that immunogenic cues related to antigenicity, costimulatory molecule expression, and inactivity of the PD-1/PD-L1 immune checkpoint likely contribute to their favorable prognosis. More aggressive ALCLs might be pharmacologically reprogrammed to a DUSP22-like, immunogenic molecular signature through the use of demethylating agents and/or immune checkpoint inhibitors.
2018-08-08 | GSE118238 | GEO
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
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