Differentially methylated regions in bipolar disorder and suicide.
Differentially methylated regions in bipolar disorder and suicide.
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DOI：
10.1002/ajmg.b.32754
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发表时间：
2019-10
期刊：
影响因子：
--
通讯作者：
Willour VL
中科院分区：
文献类型：
--
作者：
Gaine ME;Seifuddin F;Sabunciyan S;Lee RS;Benke KS;Monson ET;Zandi PP;Potash JB;Willour VL
在典型的胞嘧啶-鸟嘌呤二核苷酸(CpG)中添加甲基，就会在整个基因组中产生不同的DNA甲基化模式，从而调节基因的表达。CpG位点的DNA甲基化异常与许多精神疾病有关，包括双相情感障碍(BD)和自杀。利用SureSelectXT系统，我们研究了50例BD患者(自杀23例，其他原因27例)和31例非精神病者基因组中CpG位点的DNA甲基化状态。我们从三个分析中确定了差异甲基化区域(DMR)：(A)BD受试者与非精神病组对照(BD-NC)，(B)BD受试者与非精神病组对照(BDS-NC)，以及(C)BDS受试者与其他原因死亡的BD受试者(BDS-BDNS)比较。来自BDS-NC分析的一个DMR位于ARHGEF38，在BDS受试者中显著低甲基化(23.4%)。这一发现在多次测试(PBootstrap=9.0×10−3)后仍然显著，并通过焦磷酸测序得到验证，在男性中更为显著。二次分析利用独创性路径分析来确定名义上显著的DMR的浓缩。这确定了几个通路的关联，包括轴突引导信号、钙信号、β-肾上腺素能信号和阿片信号。我们的综合研究进一步支持DNA甲基化改变影响BD和自杀的风险。然而，需要进一步的调查来证实这些联系并确定它们的功能后果。
The addition of a methyl group to, typically, a cytosine-guanine dinucleotide (CpG) creates distinct DNA methylation patterns across the genome that can regulate gene expression. Aberrant DNA methylation of CpG sites has been associated with many psychiatric disorders including bipolar disorder (BD) and suicide. Using the SureSelectXT system, Methyl-Seq, we investigated the DNA methylation status of CpG sites throughout the genome in 50 BD individuals (23 subjects who died by suicide and 27 subjects who died from other causes) and 31 nonpsychiatric controls. We identified differentially methylated regions (DMRs) from three analyses: (a) BD subjects compared to nonpsychiatric controls (BD-NC), (b) BD subjects who died by suicide compared to nonpsychiatric controls (BDS-NC), and (c) BDS subjects compared to BD subjects who died from other causes (BDS-BDNS). One DMR from the BDS-NC analysis, located in ARHGEF38, was significantly hypomethylated (23.4%) in BDS subjects. This finding remained significant after multiple testing (PBootstrapped = 9.0 × 10−3), was validated using pyrosequencing, and was more significant in males. A secondary analysis utilized Ingenuity Pathway Analysis to identify enrichment in nominally significant DMRs. This identified an association with several pathways including axonal guidance signaling, calcium signaling, β-adrenergic signaling, and opioid signaling. Our comprehensive study provides further support that DNA methylation alterations influence the risk for BD and suicide. However, further investigation is required to confirm these associations and identify their functional consequences.
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影响因子：
3.5
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
通讯作者：
Mill J
影响因子：
1.9
作者：
Butt, Jawad H.;Dalsgaard, Soren;Fosbol, Emil L.
通讯作者：
Fosbol, Emil L.
DOI：
10.3109/15622975.2011.597875
发表时间：
2013-12
期刊：
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry
影响因子：
--
作者：
Galfalvy H;Zalsman G;Huang YY;Murphy L;Rosoklija G;Dwork AJ;Haghighi F;Arango V;Mann JJ
通讯作者：
Mann JJ
影响因子：
3.5
作者：
Gaine ME;Chatterjee S;Abel T
通讯作者：
Abel T
影响因子：
3.8
作者：
Houtepen, Lotte C.;van Bergen, Annet H.;Boks, Marco P. M.
通讯作者：
Boks, Marco P. M.