当前位置: X-MOL 学术npj Schizophr. › 论文详情
Genetic vulnerability to DUSP22 promoter hypermethylation is involved in the relation between in utero famine exposure and schizophrenia
npj Schizophrenia Pub Date : 2018-08-21 , DOI: 10.1038/s41537-018-0058-4
M. P. Boks; L. C. Houtepen; Z. Xu; Y. He; G. Ursini; A. X. Maihofer; P. Rajarajan; Q. Yu; H. Xu; Y. Wu; S. Wang; J. P. Shi; H. E. Hulshoff Pol; E. Strengman; B. P. F. Rutten; A. E. Jaffe; J. E. Kleinman; D. G. Baker; E. M. Hol; S. Akbarian; C. M. Nievergelt; L. D. De Witte; C. H. Vinkers; D. R. Weinberger; J. Yu; R. S. Kahn

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.
更新日期:2018-08-21

 

全部期刊列表>>
智控未来
聚焦商业经济政治法律
跟Nature、Science文章学绘图
控制与机器人
招募海内外科研人才,上自然官网
隐藏1h前已浏览文章
课题组网站
新版X-MOL期刊搜索和高级搜索功能介绍
ACS材料视界
x-mol收录
湖南大学化学化工学院刘松
上海有机所
廖良生
南方科技大学
西湖大学
伊利诺伊大学香槟分校
徐明华
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug