Neonatal DNA methylation and early-onset conduct problems: A genome-wide, prospective study.
Neonatal DNA methylation and early-onset conduct problems: A genome-wide, prospective study.
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DOI：
10.1017/s095457941700092x
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发表时间：
2018-05
影响因子：
3.3
通讯作者：
Barker ED
中科院分区：
文献类型：
--
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
早发性行为问题（CP）是成人犯罪和不良心理健康的关键预测因子。虽然先前的研究表明遗传和环境风险在早发性CP的发展中起重要作用，但对这些关联背后的潜在生物学过程知之甚少。在这项研究中，我们使用来自雅芳父母与儿童纵向研究（ALSPAC）的数据，研究了DNA甲基化（出生时脐带血）与CP（4-13岁）轨迹之间的前瞻性关联。基因组中7个位点的甲基化变异（FDR<0.05）区分了继续发展为早发性（n = 174）和低发性（n = 86） CP的儿童，包括MGLL附近的位点（涉及内源性大麻素信号传导和疼痛感知）。在三个候选CP基因（MAOA， BDNF和FKBP5）附近的亚阈值关联也被确定。在早发性CP组中，已识别位点的甲基化水平并不能区分儿童随着时间的推移会继续坚持或停止CP行为。总的来说，我们发现几个确定的位点与产前暴露相关，没有一个与已知的遗传mqtl相关。研究结果有助于更好地理解与早发性CP相关的表观遗传模式。
Early-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4-13yrs), using data drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC). Methylomic variation at seven loci across the genome (FDR<0.05) differentiated children who go on to develop early-onset (n = 174) vs low (n = 86) CP, including sites in the vicinity of MGLL (involved in endocannabinoid signaling and pain perception). Sub-threshold associations in the vicinity of three candidate genes for CP (MAOA, BDNF, and FKBP5) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist vs desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic mQTLs. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.