Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder.
Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder.
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DOI：
10.1093/hmg/ddr416
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发表时间：
2011-12-15
影响因子：
3.5
通讯作者：
Mill J
中科院分区：
文献类型：
--
作者：
Dempster EL;Pidsley R;Schalkwyk LC;Owens S;Georgiades A;Kane F;Kalidindi S;Picchioni M;Kravariti E;Toulopoulou T;Murray RM;Mill J
传统上，对精神分裂症（SZ）和双相情感障碍（BD）等主要精神疾病的研究主要集中在遗传和环境风险因素上，尽管最近的工作强调了表观遗传过程在介导易感性方面的额外作用。由于同卵双胞胎具有共同的DNA序列，他们的研究代表了研究表观遗传因素对疾病病因的贡献的理想设计。我们进行了一项全基因组DNA甲基化分析，该分析来自于一个独特的MZ双胞胎样本，这些样本与严重精神病不一致。许多基因座表明，双胞胎之间的疾病相关DNA甲基化差异不符合SZ和BD个体，也不符合作为联合主要精神病组的双胞胎。我们的顶级基因座的通路分析强调了与精神疾病和神经发育直接相关的生物网络和通路的表观遗传变化的显著富集。在受影响的双胞胎中，与精神病相关的差异甲基化区域位于ST6GALNAC1的启动子中，该启动子与先前报道的SZ中观察到的罕见基因组重复重叠。该位点的平均DNA甲基化差异为6%，但家族之间存在相当大的异质性，一些双胞胎的甲基化差异为20%。随后，我们在受影响个体和对照组的死后脑组织独立样本中评估了该区域，发现在一部分精神病患者中存在明显的低甲基化（>25%）。总的来说，我们的数据提供了进一步的证据，支持DNA甲基化差异在介导MZ双胞胎之间的表型差异以及SZ和BD的病因学中的作用。
Studies of the major psychoses, schizophrenia (SZ) and bipolar disorder (BD), have traditionally focused on genetic and environmental risk factors, although more recent work has highlighted an additional role for epigenetic processes in mediating susceptibility. Since monozygotic (MZ) twins share a common DNA sequence, their study represents an ideal design for investigating the contribution of epigenetic factors to disease etiology. We performed a genome-wide analysis of DNA methylation on peripheral blood DNA samples obtained from a unique sample of MZ twin pairs discordant for major psychosis. Numerous loci demonstrated disease-associated DNA methylation differences between twins discordant for SZ and BD individually, and together as a combined major psychosis group. Pathway analysis of our top loci highlighted a significant enrichment of epigenetic changes in biological networks and pathways directly relevant to psychiatric disorder and neurodevelopment. The top psychosis-associated, differentially methylated region, significantly hypomethylated in affected twins, was located in the promoter of ST6GALNAC1 overlapping a previously reported rare genomic duplication observed in SZ. The mean DNA methylation difference at this locus was 6%, but there was considerable heterogeneity between families, with some twin pairs showing a 20% difference in methylation. We subsequently assessed this region in an independent sample of postmortem brain tissue from affected individuals and controls, finding marked hypomethylation (>25%) in a subset of psychosis patients. Overall, our data provide further evidence to support a role for DNA methylation differences in mediating phenotypic differences between MZ twins and in the etiology of both SZ and BD.
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影响因子：
3.7
作者：
Bocklandt S;Lin W;Sehl ME;Sánchez FJ;Sinsheimer JS;Horvath S;Vilain E
通讯作者：
Vilain E
DOI：
10.1523/jneurosci.1786-08.2008
发表时间：
2008-10-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lubin FD;Roth TL;Sweatt JD
通讯作者：
Sweatt JD
DOI：
10.1124/jpet.104.081711
发表时间：
2005-05-01
影响因子：
3.5
作者：
Chaki, S;Funakoshi, T;Thomsen, W
通讯作者：
Thomsen, W
DOI：
10.1002/ajmg.b.31192
发表时间：
2011-07-01
影响因子：
2.8
作者：
Ghadirivasfi, Mohammad;Nohesara, Shabnam;Abdolmaleky, Hamid Mostafavi
通讯作者：
Abdolmaleky, Hamid Mostafavi
影响因子：
64.5
作者：
Ballas, N;Grunseich, C;Mandel, G
通讯作者：
Mandel, G