Prenatal nutrition, epigenetics and schizophrenia risk: can we test causal effects?
Prenatal nutrition, epigenetics and schizophrenia risk: can we test causal effects?
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DOI：
10.2217/epi.12.20
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发表时间：
2012-06
期刊：
影响因子：
3.8
通讯作者：
Relton CL
中科院分区：
文献类型：
--
作者：
Kirkbride JB;Susser E;Kundakovic M;Kresovich JK;Davey Smith G;Relton CL
我们认为母亲产前营养可以通过表观遗传效应影响后代精神分裂症的风险。在这篇文章中，我们认为有证据表明，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，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干扰产前营养和随后的精神分裂症的风险之间的途径的调解人。虽然人类死后的研究证明了精神分裂症患者大脑中DNA甲基化的变化，但这些研究无法建立因果关系。我们提出了一个可检验的假设，利用一种新的两步孟德尔随机化方法，以测试的组成部分，拟议的因果途径导致产前营养暴露精神分裂症。在这里应用到一个具体的例子，这样的方法是适用于更广泛的使用，以加强因果推理的中介作用的表观遗传因素联系在一起，以人口为基础的研究中的健康结果的暴露。
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.