The Future is The Past: Methylation QTLs in Schizophrenia.
The Future is The Past: Methylation QTLs in Schizophrenia.
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DOI：
10.3390/genes7120104
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发表时间：
2016-11-24
期刊：
影响因子：
3.5
通讯作者：
Spengler D
中科院分区：
文献类型：
--
作者：
Hoffmann A;Ziller M;Spengler D
全基因组关联研究（GWAS）对精神分裂症（SCZ）的遗传基础有着显著的进步。尽管如此，疾病风险的大部分功能差异仍然无法解释。因此，越来越需要将遗传变异性映射到基因功能，以了解SCZ的病理生理学和开发更好的治疗方法。遗传变异可以调节各种细胞功能，包括DNA甲基化，一种在转录和环境影响中起重要作用的表观遗传标记。甲基化数量性状基因座（meQTL）是通过对遗传上不同的基因型个体的DNA甲基化水平进行定位而得到的，并定义了DNA甲基化受遗传变异影响的基因座。最近的证据表明，脑组织中存在丰富的meQTL，其对发育和精神疾病的功能贡献仍然知之甚少。有趣的是，胎儿meQTLs驻留在调控结构域影响甲基化组重构在早期脑发育和富集的基因座确定的GWAS SCZ。此外，胎儿meQTL保存在成人大脑中，可以跟踪脆弱时期的早期表观基因组失调。总体而言，这些发现强调了胎儿meQTL在SCZ遗传风险和可能的神经发育起源中的作用。
Genome-wide association studies (GWAS) have remarkably advanced insight into the genetic basis of schizophrenia (SCZ). Still, most of the functional variance in disease risk remains unexplained. Hence, there is a growing need to map genetic variability-to-genes-to-functions for understanding the pathophysiology of SCZ and the development of better treatments. Genetic variation can regulate various cellular functions including DNA methylation, an epigenetic mark with important roles in transcription and the mediation of environmental influences. Methylation quantitative trait loci (meQTLs) are derived by mapping levels of DNA methylation in genetically different, genotyped individuals and define loci at which DNA methylation is influenced by genetic variation. Recent evidence points to an abundance of meQTLs in brain tissues whose functional contributions to development and mental diseases are still poorly understood. Interestingly, fetal meQTLs reside in regulatory domains affecting methylome reconfiguration during early brain development and are enriched in loci identified by GWAS for SCZ. Moreover, fetal meQTLs are preserved in the adult brain and could trace early epigenomic deregulation during vulnerable periods. Overall, these findings highlight the role of fetal meQTLs in the genetic risk for and in the possible neurodevelopmental origin of SCZ.
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遗传和表观遗传变异对基因调节和剪接的组织特异性作用。
影响因子：
4.5
作者：
Gutierrez-Arcelus M;Ongen H;Lappalainen T;Montgomery SB;Buil A;Yurovsky A;Bryois J;Padioleau I;Romano L;Planchon A;Falconnet E;Bielser D;Gagnebin M;Giger T;Borel C;Letourneau A;Makrythanasis P;Guipponi M;Gehrig C;Antonarakis SE;Dermitzakis ET
通讯作者：
Dermitzakis ET
影响因子：
64.5
作者：
Gifford CA;Ziller MJ;Gu H;Trapnell C;Donaghey J;Tsankov A;Shalek AK;Kelley DR;Shishkin AA;Issner R;Zhang X;Coyne M;Fostel JL;Holmes L;Meldrim J;Guttman M;Epstein C;Park H;Kohlbacher O;Rinn J;Gnirke A;Lander ES;Bernstein BE;Meissner A
通讯作者：
Meissner A
影响因子：
16.2
作者：
Arloth J;Bogdan R;Weber P;Frishman G;Menke A;Wagner KV;Balsevich G;Schmidt MV;Karbalai N;Czamara D;Altmann A;Trümbach D;Wurst W;Mehta D;Uhr M;Klengel T;Erhardt A;Carey CE;Conley ED;Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (PGC);Ruepp A;Müller-Myhsok B;Hariri AR;Binder EB;Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium PGC
通讯作者：
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium PGC
影响因子：
4.5
作者：
Gertz J;Varley KE;Reddy TE;Bowling KM;Pauli F;Parker SL;Kucera KS;Willard HF;Myers RM
通讯作者：
Myers RM
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium