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

Autor: Dewleen G. Baker, Christiaan H. Vinkers, Eric Strengman, Daniel R. Weinberger, Hilleke E. Hulshoff Pol, Lotte C Houtepen, Elly M. Hol, Bart P. F. Rutten, Caroline M. Nievergelt, Y Wu, Adam X. Maihofer, L D de Witte, Qiong Yu, J Yu, H Xu, Jieping Shi, Joel E. Kleinman, Yujie He, S Wang, Andrew E. Jaffe, Schahram Akbarian, Prashanth Rajarajan, Marco P. Boks, Gianluca Ursini, Z. Xu, R.S. Kahn
Přispěvatelé: Molecular cell biology and Immunology, APH - Mental Health
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Boks, M P, Houtepen, L C, Xu, Z, He, Y, Ursini, G, Maihofer, A X, Rajarajan, P, Yu, Q, Xu, H, Wu, Y, Wang, S, Shi, J P, Hulshoff Pol, H E, Strengman, E, Rutten, B P F, Jaffe, A E, Kleinman, J E, Baker, D G, Hol, E M, Akbarian, S, Nievergelt, C M, De Witte, L D, Vinkers, C H, Weinberger, D R, Yu, J & Kahn, R S 2018, ' Genetic vulnerability to DUSP22 promoter hypermethylation is involved in the relation between in utero famine exposure and schizophrenia ', Schizophrenia Research, vol. 4, no. 1, pp. 16 . https://doi.org/10.1038/s41537-018-0058-4
npj Schizophrenia, Vol 4, Iss 1, Pp 1-8 (2018)
npj Schizophrenia, 4(1). Nature Publishing Group
NPJ Schizophrenia
Schizophrenia Research, 4(1). Elsevier
ISSN: 1687-2932
2334-265X
Popis: 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.
Databáze: OpenAIRE
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