Cell-specific histone modification maps in the human frontal lobe link schizophrenia risk to the neuronal epigenome.
Cell-specific histone modification maps in the human frontal lobe link schizophrenia risk to the neuronal epigenome.
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DOI：
10.1038/s41593-018-0187-0
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发表时间：
2018-08
影响因子：
25
通讯作者：
Akbarian S
中科院分区：
文献类型：
--
作者：
Girdhar K;Hoffman GE;Jiang Y;Brown L;Kundakovic M;Hauberg ME;Francoeur NJ;Wang YC;Shah H;Kavanagh DH;Zharovsky E;Jacobov R;Wiseman JR;Park R;Johnson JS;Kassim BS;Sloofman L;Mattei E;Weng Z;Sieberts SK;Peters MA;Harris BT;Lipska BK;Sklar P;Roussos P;Akbarian S
精神分裂症的风险变异影响 100 多个基因组位点，但疾病易感性背后的细胞和组织特异性作用仍然知之甚少。我们针对与精神病有关的两个皮质区域（背外侧前额叶皮质和前扣带皮层），从神经元、神经元耗尽和大量组织染色质中生成了 157 个参考图谱，用于与活性启动子和增强子相关的两个组蛋白标记，即 H3-三甲基赖氨酸 4 (H3K4me3) 和 H3-乙酰基赖氨酸 27 （H3K27ac）。神经元和神经元耗尽的染色质状态之间的差异是组蛋白修饰谱变化的主轴，其次是受试者和皮质区域之间的显着变化。在神经元和神经元耗尽的样本中鉴定出数千个重要的组蛋白数量性状基因座（hQTL）。精神分裂症、抑郁症状和神经质的风险变异在神经元 H3K4me3 和 H3K27ac 景观中显着过高。我们的 PsychENCODE 和 CommonMind 赞助的资源强调了细胞类型特异性特征在人类额叶调节和疾病相关非编码序列中的关键作用。
Risk variants for schizophrenia affect more than 100 genomic loci, yet cell- and tissue-specific roles underlying disease liability remain poorly characterized. We have generated for two cortical areas implicated in psychosis, dorsolateral prefrontal cortex and anterior cingulate cortex, 157 reference maps from neuronal, neuronal-depleted and bulk tissue chromatin for two histone marks associated with active promoters and enhancers, H3-trimethyl-lysine 4 (H3K4me3) and H3-acetyl-lysine 27 (H3K27ac). Differences between neuronal and neuronal-depleted chromatin states were the major axis of variation in histone modification profiles followed by substantial variability across subjects and cortical areas. Thousands of significant histone quantitative trait loci (hQTLs) were identified in neuronal and neuronal-depleted samples. Risk variants for schizophrenia, depressive symptoms and neuroticism were significantly overrepresented in neuronal H3K4me3 and H3K27ac landscapes. Our PsychENCODE and CommonMind sponsored resource highlights the critical role of cell-type specific signatures at regulatory and disease-associated non-coding sequences in the human frontal lobe.
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影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
DOI：
10.1093/bioinformatics/btv562
发表时间：
2016-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Gel B;Díez-Villanueva A;Serra E;Buschbeck M;Peinado MA;Malinverni R
通讯作者：
Malinverni R
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3.5
作者：
Griswold, Anthony J.;Ma, Deqiong;Pericak-Vance, Margaret A.
通讯作者：
Pericak-Vance, Margaret A.
影响因子：
3
作者：
Hoffman GE;Schadt EE
通讯作者：
Schadt EE