吸烟和血液DNA甲基化之间的单向和双向因果关系:基于双胞胎的孟德尔随机化的证据
Madhurbain Singh1,2,3, Conor V Dolan3,4,5, Dana M Lapato1,2
1Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
medRxiv : the preprint server for health sciences
|July 1, 2024
概括
吸烟对500多个血液部位的DNA甲基化 (DNAm) 有因果影响,这可能解释吸烟相关的健康问题. DNAm变异也可能影响吸烟行为,揭示双向联系.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因组学就是基因组学.
- 行为科学 行为科学
背景情况:
- 吸烟与DNA甲基化 (DNAm) 变化有关,被认为会导致不良健康影响.
- 之前的孟德尔随机化 (MR) 研究发现吸烟对DNAm的因果影响的证据有限.
研究的目的:
- 通过使用综合MR和双因果模型方法,研究当前吸烟和血液DNAm之间的因果关系.
- 探索DNA甲基化和吸烟责任之间的潜在双向因果关系.
主要方法:
- 利用了来自荷兰双胞胎登记的数据 (N=2577).
- 采用了组合的孟德尔随机化 (MR) 和双因果模型.
- 使用多基/多基因分数作为仪器变量,控制水平基.
主要成果:
- 鉴定了当前吸烟对DNAm在>500位点的潜在因果影响,丰富了血液形成和免疫调节等途径.
- 发现了反向和双向因果关系的证据,其中DNAm变异可能会影响吸烟责任.
- 在大脑中发现了与影响吸烟的DNAm相关的特定基因调节元件,并确定了参与G蛋白结合受体信号传递和天生的免疫力中的基因.
结论:
- 这项研究提供了强有力的证据,证明目前的吸烟和血液DNAm之间存在因果关系.
- 突出了DNA甲基化和吸烟行为之间的复杂相互作用,包括双向效应.
- 证明了双胞胎研究与基因型和DNAm数据的实用性,用于表观遗传学和健康的因果推断.
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