Jensen Dawn, Chen Jiayu, Turner Jessica A, Stephen Julia M, Wang Yu-Ping, Wilson Tony W, Calhoun Vince D, Liu Jingyu
Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS): (Georgia State University, Georgia Institute of Technology, and Emory University), Atlanta, GA, United States.
Neuroscience Institute, Georgia State University, Atlanta, GA, United States.
Front Genet. 2025 Jan 7;15:1451150. doi: 10.3389/fgene.2024.1451150. eCollection 2024.
Typical adolescent neurodevelopment is marked by decreases in grey matter (GM) volume, increases in myelination, measured by fractional anisotropy (FA), and improvement in cognitive performance.
To understand how epigenetic changes, methylation (DNAm) in particular, may be involved during this phase of development, we studied cognitive assessments, DNAm from saliva, and neuroimaging data from a longitudinal cohort of normally developing adolescents, aged nine to fourteen. We extracted networks of methylation with patterns of correlated change using a weighted gene correlation network analysis (WCGNA). Modules from these analyses, consisting of co-methylation networks, were then used in multivariate analyses with GM, FA, and cognitive measures to assess the nature of their relationships with cognitive improvement and brain development in adolescence.
This longitudinal exploration of co-methylated networks revealed an increase in correlated epigenetic changes as subjects progressed into adolescence. Co-methylation networks enriched for pathways involved in neuronal systems, potassium channels, neurexins and neuroligins were both conserved across time as well as associated with maturation patterns in GM, FA, and cognition.
Our research shows that correlated changes in the DNAm of genes in neuronal processes involved in adolescent brain development that were both conserved across time and related to typical cognitive and brain maturation, revealing possible epigenetic mechanisms driving this stage of development.
典型的青少年神经发育的特征是灰质（GM）体积减少、髓鞘形成增加（通过分数各向异性（FA）衡量）以及认知能力提高。
为了解表观遗传变化，特别是甲基化（DNAm）在这一发育阶段可能如何起作用，我们研究了正常发育的9至14岁青少年纵向队列的认知评估、唾液中的DNAm以及神经影像学数据。我们使用加权基因共表达网络分析（WCGNA）提取了具有相关变化模式的甲基化网络。然后，将这些分析中由共甲基化网络组成的模块用于与GM、FA和认知指标的多变量分析，以评估它们与青少年认知改善和大脑发育之间关系的性质。
对共甲基化网络的纵向探索显示，随着受试者进入青春期，相关的表观遗传变化增加。富含神经元系统、钾通道、神经纤毛蛋白和神经连接蛋白相关通路的共甲基化网络在时间上是保守的，并且与GM、FA和认知的成熟模式相关。
我们的研究表明，参与青少年大脑发育的神经元过程中基因的DNAm相关变化在时间上是保守的，并且与典型的认知和大脑成熟相关，揭示了驱动这一发育阶段的可能表观遗传机制。
