Spencer Sophie, Harker Samantha A, Barry Fatoumata, Beauchemin Jennifer, Braden B Blair, Burton Phoebe, D'sa Viren, Koinis-Mitchell Daphne, Mennenga Sarah E, Deoni Sean C L, Lewis Candace R
Arizona State University.
Rhode Island Hospital, Brown University.
Res Sq. 2024 Apr 19:rs.3.rs-4139933. doi: 10.21203/rs.3.rs-4139933/v1.
Epigenetic processes, including DNA methylation, are emerging as key areas of interest for their potential roles as biomarkers and contributors to the risk of neurodevelopmental, psychiatric, and other brain-based disorders. Despite this growing focus, there remains a notable gap in our understanding of how DNA methylation correlates with individual variations in brain function and structure. Additionally, the dynamics of these relationships during developmental periods, which are critical windows during which many disorders first appear, are still largely unexplored. The current study extends the field by examining if peripheral DNA methylation of myelination-related genes predicts white matter volume in a healthy pediatric population [N = 250; females = 113; age range 2 months-14 years; = 5.14, = 3.60]. We assessed if DNA methylation of 17 myelin-related genes predict white matter volume and if age moderates these relationships. Results highlight low variability in myelin-related epigenetic variance at birth, which rapidly increases non-linearly with age, and that DNA methylation, measured at both the level of a CpG site or gene, is highly predictive of white matter volume, in early childhood but not late childhood. These novel findings propel the field forward by establishing that DNA methylation of myelin-related genes from a peripheral tissue is a predictive marker of white matter volume in children and is influenced by developmental stage. The research underscores the significance of peripheral epigenetic patterns as a proxy for investigating the effects of environmental factors, behaviors, and disorders associated with white matter.
表观遗传过程，包括DNA甲基化，正成为备受关注的关键领域，因为它们作为生物标志物以及导致神经发育、精神和其他脑部疾病风险的潜在作用。尽管关注度不断提高，但我们对DNA甲基化如何与脑功能和结构的个体差异相关联的理解仍存在显著差距。此外，在发育阶段这些关系的动态变化，而发育阶段是许多疾病首次出现的关键时期，目前仍 largely 未被探索。本研究通过检查髓鞘形成相关基因的外周DNA甲基化是否能预测健康儿童群体的白质体积 [N = 250；女性 = 113；年龄范围2个月至14岁；= 5.14，= 3.60] 来扩展该领域。我们评估了17个髓鞘形成相关基因的DNA甲基化是否能预测白质体积，以及年龄是否会调节这些关系。结果表明，出生时髓鞘形成相关表观遗传变异的变异性较低，随年龄迅速非线性增加，并且在儿童早期而非晚期，无论是在CpG位点还是基因水平测量的DNA甲基化对白质体积都具有高度预测性。这些新发现通过确定外周组织中髓鞘形成相关基因的DNA甲基化是儿童白质体积的预测标志物且受发育阶段影响，推动了该领域的发展。该研究强调了外周表观遗传模式作为研究与白质相关的环境因素、行为和疾病影响的代理指标的重要性。
