DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.
DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.
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DNA甲基化特征的侵略和密切相关的结构：荟萃分析表观基因组研究在整个生命周期。
DOI：
10.1038/s41380-020-00987-x
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发表时间：
2021-06
影响因子：
11
通讯作者：
Boomsma DI
中科院分区：
文献类型：
--
作者：
van Dongen J;Hagenbeek FA;Suderman M;Roetman PJ;Sugden K;Chiocchetti AG;Ismail K;Mulder RH;Hafferty JD;Adams MJ;Walker RM;Morris SW;Lahti J;Küpers LK;Escaramis G;Alemany S;Jan Bonder M;Meijer M;Ip HF;Jansen R;Baselmans BML;Parmar P;Lowry E;Streit F;Sirignano L;Send TS;Frank J;Jylhävä J;Wang Y;Mishra PP;Colins OF;Corcoran DL;Poulton R;Mill J;Hannon E;Arseneault L;Korhonen T;Vuoksimaa E;Felix JF;Bakermans-Kranenburg MJ;Campbell A;Czamara D;Binder E;Corpeleijn E;Gonzalez JR;Grazuleviciene R;Gutzkow KB;Evandt J;Vafeiadi M;Klein M;van der Meer D;Ligthart L;BIOS Consortium;Kluft C;Davies GE;Hakulinen C;Keltikangas-Järvinen L;Franke B;Freitag CM;Konrad K;Hervas A;Fernández-Rivas A;Vetro A;Raitakari O;Lehtimäki T;Vermeiren R;Strandberg T;Räikkönen K;Snieder H;Witt SH;Deuschle M;Pedersen NL;Hägg S;Sunyer J;Franke L;Kaprio J;Ollikainen M;Moffitt TE;Tiemeier H;van IJzendoorn MH;Relton C;Vrijheid M;Sebert S;Jarvelin MR;Caspi A;Evans KL;McIntosh AM;Bartels M;Boomsma DI
攻击行为的DNA甲基化谱可以捕获与攻击相关的遗传、随机和环境影响的终生累积效应。在这里，我们报告了攻击行为的表观基因组关联研究（EWAS）的第一个大型荟萃分析（N = 15,324名参与者）。在来自18个平均年龄在7至68岁的队列的14434名参与者的外周血样本中，13个甲基化位点与攻击性显著相关（alpha = 1.2 × 10−7；Bonferroni校正）。在来自5个队列的2425名儿童的脐带血样本中，平均年龄在4 - 7岁之间，83%的这些位点显示出与儿童攻击的相同方向（r = 0.74, p = 0.006），但没有发现表观基因组范围内的显著位点。顶位位点（在外周血荟萃分析或外周血和脐带血联合荟萃分析中有48个错误发现率为5%）与化学物质暴露、吸烟、认知、代谢特征和遗传变异（mqtl）有关。三个表达水平与顶位点相关的基因先前与精神分裂症和一般风险承受能力有关。在6个CpGs中，血液中的DNA甲基化变化反映了大脑中的变化。平均44%（范围= 3-82%）的攻击性-甲基化关联可以用当前和以前的吸烟和BMI来解释。这些发现指向了对化学暴露敏感的位点，对神经元功能有潜在的影响。我们希望这些结果能够成为研究的起点，从而应用于外围生物标志物，并揭示与攻击和相关特征的因果关系。
DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
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影响因子：
3.3
作者：
Cecil CAM;Walton E;Jaffee SR;O'Connor T;Maughan B;Relton CL;Smith RG;McArdle W;Gaunt TR;Ouellet-Morin I;Barker ED
通讯作者：
Barker ED
DOI：
10.1176/appi.ajp.2018.17060595
发表时间：
2018-08-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Han LKM;Aghajani M;Clark SL;Chan RF;Hattab MW;Shabalin AA;Zhao M;Kumar G;Xie LY;Jansen R;Milaneschi Y;Dean B;Aberg KA;van den Oord EJCG;Penninx BWJH
通讯作者：
Penninx BWJH
影响因子：
0.9
作者：
Kaprio, Jaakko
通讯作者：
Kaprio, Jaakko
影响因子：
0.9
作者：
Boomsma, Dorret I.;de Geus, Eco J. C.;Willemsen, Gonneke
通讯作者：
Willemsen, Gonneke
影响因子：
7.7
作者：
L'Abee, Carianne;Sauer, Pieter J. J.;Stolk, Ronald P.
通讯作者：
Stolk, Ronald P.