Brain Research Institute, University of Zurich/Swiss Federal Institute of Technology, Zurich, Switzerland.
Biol Psychiatry. 2013 Feb 15;73(4):313-20. doi: 10.1016/j.biopsych.2012.08.019. Epub 2012 Oct 9.
Psychiatric diseases are multifaceted disorders with complex etiology, recognized to have strong heritable components. Despite intense research efforts, genetic loci that substantially account for disease heritability have not yet been identified. Over the last several years, epigenetic processes have emerged as important factors for many brain diseases, and the discovery of epigenetic processes in germ cells has raised the possibility that they may contribute to disease heritability and disease risk. This review examines epigenetic mechanisms in complex diseases and summarizes the most illustrative examples of transgenerational epigenetic inheritance in mammals and their relevance for brain function. Environmental factors that can affect molecular processes and behavior in exposed individuals and their offspring, and their potential epigenetic underpinnings, are described. Possible routes and mechanisms of transgenerational transmission are proposed, and the major questions and challenges raised by this emerging field of research are considered.
精神疾病是具有复杂病因的多方面障碍,被认为具有很强的遗传成分。尽管进行了大量的研究,但尚未确定能在很大程度上解释疾病遗传性的遗传位点。在过去的几年中,表观遗传过程已成为许多脑部疾病的重要因素,而在生殖细胞中发现的表观遗传过程提出了这样一种可能性,即它们可能有助于疾病遗传性和疾病风险。本文综述了复杂疾病中的表观遗传机制,并总结了哺乳动物中具有代表性的跨代表观遗传遗传实例及其对大脑功能的相关性。描述了可影响暴露个体及其后代的分子过程和行为的环境因素,以及它们潜在的表观遗传基础。提出了跨代传递的可能途径和机制,并考虑了这一新兴研究领域提出的主要问题和挑战。