基因甲基化作为可能连接童年逆境和健康的机制:来自两样本孟德尔随机化研究的结果
Isabel K Schuurmans1,2, Erin C Dunn1,3,4, Alexandre A Lussier1,3,4
1Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, United States.
American journal of epidemiology
|May 16, 2024
概括
童年逆境通过DNA甲基化 (DNAm) 影响健康. 早期的DNAm变化与精神和身体健康问题有因果关系,可能充当保护机制.
科学领域:
- 健康和疾病的表观遗传学和发育起源 (DOHaD).
背景情况:
- 童年逆境是终身健康问题的重要风险因素.
- 人们假设表观遗传修饰,特别是DNA甲基化 (DNAm),可以调解逆境和疾病易感性之间的联系.
- 有限的研究存在于与逆境相关的DNAm变化的因果关系和发育时间.
研究的目的:
- 调查与逆境相关的DNA甲基化位点在发育阶段 (出生,童年,青春期,青春期) 和24个心理,身体和行为健康结果之间的因果关系.
- 确定DNAm变化的发育时间是否影响它们与健康结果的关系.
主要方法:
- 使用双样本门德尔随机化 (MR) 进行强大的因果推理.
- 检查了与童年逆境相关的DNA甲基化位点.
- 评估了与24个不同健康结果的关联,跨越了生命周期.
主要成果:
- 确定了与逆境相关的DNAm和注意力缺陷/多动症障碍,抑郁症,强迫症障碍,自杀企图,喘,冠状动脉疾病和慢性病之间的显著因果关联.
- 与青少年和年轻成年人相比,在出生和童年时发现了mDNA的更强的关联.
- 观察到儿童DNAm loci主要表现出与健康结果的风险抑制关系,这表明潜在的缓冲效应.
结论:
- 与逆境相关的DNA甲基化变化与身体和心理健康结果有因果关系.
- DNAm差异对健康的影响尤其明显,当变化在发育早期 (出生和童年) 出现时.
- 儿童DNAm可能起到补偿或保护作用,防止早期逆境的不良影响,而不是仅仅表明疾病风险.
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