Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis.
Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis.
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DNA甲基化与从出生到学龄ADHD症状之间的关系：一项前瞻性荟萃分析
DOI：
10.1038/s41398-020-01058-z
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发表时间：
2020-11-12
影响因子：
6.8
通讯作者：
Tiemeier H
中科院分区：
文献类型：
--
作者：
Neumann A;Walton E;Alemany S;Cecil C;González JR;Jima DD;Lahti J;Tuominen ST;Barker ED;Binder E;Caramaschi D;Carracedo Á;Czamara D;Evandt J;Felix JF;Fuemmeler BF;Gutzkow KB;Hoyo C;Julvez J;Kajantie E;Laivuori H;Maguire R;Maitre L;Murphy SK;Murcia M;Villa PM;Sharp G;Sunyer J;Raikkönen K;Bakermans-Kranenburg M;IJzendoorn MV;Guxens M;Relton CL;Tiemeier H
注意力缺陷多动障碍（ADHD）是一种常见的儿童疾病，具有很大的遗传因素。然而，表观遗传机制在该疾病的病因学中发挥作用的程度尚不清楚。我们在妊娠和儿童表观遗传学 (PACE) 联盟内进行了全表观基因组关联研究 (EWAS)，以确定在两个甲基化评估阶段（出生和学龄）与 ADHD 症状相关的 DNA 甲基化位点。我们研究了来自 5 个队列的 2477 名儿童的脐带血 DNA 甲基化与反复评估的 ADHD 症状（4-15 岁）的关联，以及来自 9 个队列的 2374 名儿童的学龄 DNA 甲基化与并发 ADHD 症状（7-11 岁）的关联，其中 3 个队列在两个时间点都参与。在任一 EWAS 中具有名义显着性 (p<0.05) 的 CpG 在时间点之间相关 (ρ=0.30)，表明关联存在重叠；然而，主要信号却截然不同。出生时，我们确定了 9 个可预测以后 ADHD 症状的 CpG (p < 1 × 10–7)，包括 ERC2 和 CREB5。这些 CpG 之一（ERC2 启动子区域的 cg01271805，调节神经递质释放）的外周血 DNA 甲基化先前被认为与大脑甲基化有关。另一个（cg25520701）位于 CREB5 基因体内，该基因先前与神经突生长和 ADHD 诊断相关。相比之下，在学龄期，没有 CpG 与 ADHD 相关，p < 1 × 10−7。总之，我们在这项研究中发现了出生时 DNA 甲基化与 ADHD 相关的证据。未来的研究需要证实甲基化变异作为生物标志物的效用及其在因果途径中的参与。
Attention-deficit and hyperactivity disorder (ADHD) is a common childhood disorder with a substantial genetic component. However, the extent to which epigenetic mechanisms play a role in the etiology of the disorder is unknown. We performed epigenome-wide association studies (EWAS) within the Pregnancy And Childhood Epigenetics (PACE) Consortium to identify DNA methylation sites associated with ADHD symptoms at two methylation assessment periods: birth and school age. We examined associations of both DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age 4–15 years) in 2477 children from 5 cohorts and of DNA methylation at school age with concurrent ADHD symptoms (age 7–11 years) in 2374 children from 9 cohorts, with 3 cohorts participating at both timepoints. CpGs identified with nominal significance (p < 0.05) in either of the EWAS were correlated between timepoints (ρ = 0.30), suggesting overlap in associations; however, top signals were very different. At birth, we identified nine CpGs that predicted later ADHD symptoms (p < 1 × 10–7), including ERC2 and CREB5. Peripheral blood DNA methylation at one of these CpGs (cg01271805 in the promoter region of ERC2, which regulates neurotransmitter release) was previously associated with brain methylation. Another (cg25520701) lies within the gene body of CREB5, which previously was associated with neurite outgrowth and an ADHD diagnosis. In contrast, at school age, no CpGs were associated with ADHD with p < 1 × 10−7. In conclusion, we found evidence in this study that DNA methylation at birth is associated with ADHD. Future studies are needed to confirm the utility of methylation variation as biomarker and its involvement in causal pathways.
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患有和不患有注意力缺陷多动障碍（ADHD）的青少年在执行持续注意力任务期间大脑激活随时间的差异模式。
影响因子：
1.4
作者：
Epstein JN;Delbello MP;Adler CM;Altaye M;Kramer M;Mills NP;Strakowski SM;Holland S
通讯作者：
Holland S
影响因子：
5.3
作者：
Franke B;Neale BM;Faraone SV
通讯作者：
Faraone SV
影响因子：
2.1
作者：
Hong, Jaeyoung;Lunetta, Kathryn L.;Liu, Ching-Ti
通讯作者：
Liu, Ching-Ti
影响因子：
11
作者：
Cecil, C. A. M.;Lysenko, L. J.;Jaffee, S. R.;Pingault, J-B;Smith, R. G.;Relton, C. L.;Woodward, G.;McArdle, W.;Mill, J.;Barker, E. D.
通讯作者：
Barker, E. D.
DOI：
10.1002/ajmg.b.32323
发表时间：
2015-07-01
影响因子：
2.8
作者：
Hatzimanolis, Alex;Bhatnagar, Pallav;Avramopoulos, Dimitrios
通讯作者：
Avramopoulos, Dimitrios