抑郁的多基因遗传基础

The polygenic underpinnings of depression

抑郁具有复杂的、非孟德尔式的多基因遗传模式,但是目前多数抑郁的遗传研究集中于考察单个候选基因,不能全面揭示遗传因素的作用机制。近年来,多基因遗传得分研究和基因-基因交互研究分别为抑郁的多基因累加效应和交互效应提供了新的证据。多基因不仅直接影响抑郁,还通过与环境因素的交互作用影响抑郁的发生发展,并且这一复杂交互作用存在性别差异。抑郁的内表型研究发现多基因可能通过认知因素、人格、压力荷尔蒙等间接影响个体的抑郁水平。未来研究应更加关注多基因与多种环境因素如何相互作用影响抑郁,探索多基因遗传机制的性别差异,考察多基因对抑郁影响随年龄的发展动态变化。

Depression has highly complicated polygenic underpinnings that do not follow the law of Mendelian inheritance. However, existing research on the genetic mechanism of depression has primarily focused on the effects of single candidate genes. Recent studies using the method of polygenic risk scores and the gene by gene interactions approach have provided new evidence respectively for the existence of both additive genetic effects and interactive genetic effects on depression. These studies demonstrated that multi- genes interact with environmental factors in their effects on the etiology of depression, and gender has a strong influence on these interactions. It is assumed that the effects of multi-genes on depression would be possibly mediated by the specific endophenotypes, such as cognitive factors, personality and stress hormone. Future research in this realm should pay greater attention to the interactions between multi-genes and multi-environments, gender differences in the polygenic underpinnings and the dynamic changes in polygenic effects over development.