EpiCentre group, Department of Psychiatry, University of Cambridge, Herchel Smith Building for Brain & Mind Sciences, Forvie Site, Robinson Way, Cambridge, UK.
Epigenomics. 2012 Jun;4(3):303-15. doi: 10.2217/epi.12.20.
We posit that maternal prenatal nutrition can influence offspring schizophrenia risk via epigenetic effects. In this article, we consider evidence that prenatal nutrition is linked to epigenetic outcomes in offspring and schizophrenia in offspring, and that schizophrenia is associated with epigenetic changes. We focus upon one-carbon metabolism as a mediator of the pathway between perturbed prenatal nutrition and the subsequent risk of schizophrenia. Although post-mortem human studies demonstrate DNA methylation changes in brains of people with schizophrenia, such studies cannot establish causality. We suggest a testable hypothesis that utilizes a novel two-step Mendelian randomization approach, to test the component parts of the proposed causal pathway leading from prenatal nutritional exposure to schizophrenia. Applied here to a specific example, such an approach is applicable for wider use to strengthen causal inference of the mediating role of epigenetic factors linking exposures to health outcomes in population-based studies.
我们假设，母体产前营养可以通过表观遗传效应影响后代患精神分裂症的风险。在本文中，我们考虑了以下证据：产前营养与后代的表观遗传结果和后代的精神分裂症有关，而精神分裂症与表观遗传变化有关。我们专注于一碳代谢作为扰乱产前营养与随后精神分裂症风险之间途径的中介。尽管尸检人类研究表明精神分裂症患者大脑中的 DNA 甲基化发生了变化，但这些研究并不能确定因果关系。我们提出了一个可检验的假设，该假设利用了一种新的两步孟德尔随机化方法，来测试从产前营养暴露到精神分裂症的拟议因果途径的组成部分。在这里，我们将这种方法应用于一个具体的例子，这种方法可广泛应用于加强基于人群的研究中，以确定将暴露与健康结果联系起来的表观遗传因素的中介作用的因果推断。
