荷兰阿姆斯特丹大学Eske M. Derks团队，采用多组织转录组分析鉴定了神经精神病特征的遗传机制。这一研究成果于2019年6月发表在国际学术期刊《Nature Genetics》上。

研究表明，精神疾病的遗传结构特点在于大量的主要位于非编码区的小效应变异体, 表明潜在的致病效应可能通过调节基因表达来影响疾病风险。该团队研究人员首次依据多组织转录组数据提供了全面的分析，以获得对精神疾病中大脑，神经内分泌因子（肾上腺）和胃肠系统（结肠）作用的病理生理学认知。在每个组织中，研究人员执行PrediXcan分析并鉴定出精神分裂症（n关联= 499; n独特基因= 275），双相情感障碍（n关联= 17; n独特基因= 13），注意力缺陷多动障碍（n关联= 19; n独特基因= 12）和广泛抑郁（n关联= 41; n独特基因= 31）的特征相关基因。重要的是，PrediXcan与基于汇总数据的孟德尔随机化分析/依赖仪器的异质性分析均提示非脑组织中存在潜在的致病基因，表明这些组织具有绘制精神疾病遗传易感性的效用。他们的分析进一步强调联合组织探讨的重要性，因为76％的基因仅在难以获得的组织中被检测到。

附：英文原文

Title: Multi-tissue transcriptome analyses identify genetic mechanisms underlying neuropsychiatric traits

Author: Eric R. Gamazon, Aeilko H. Zwinderman, Nancy J. Cox, Damiaan Denys, Eske M. Derks

Issue&Volume:Volume 51 Issue 6, June 2019

Abstract: The genetic architecture of psychiatric disorders is characterized by a large number of small-effect variants1 located primarily in non-coding regions, suggesting that the underlying causal effects may influence disease risk by modulating gene expression24. We provide comprehensive analyses using transcriptome data from an unprecedented collection of tissues to gain pathophysiological insights into the role of the brain, neuroendocrine factors (adrenal gland) and gastrointestinal systems (colon) in psychiatric disorders. In each tissue, we perform PrediXcan analysis and identify trait-associated genes for schizophrenia (n associations=499; n unique genes=275), bipolar disorder (n associations=17; n unique genes=13), attention deficit hyperactivity disorder (n associations=19; n unique genes=12) and broad depression (n associations=41; n unique genes=31). Importantly, both PrediXcan and summary-data-based Mendelian randomization/heterogeneity in dependent instruments analyses suggest potentially causal genes in non-brain tissues, showing the utility of these tissues for mapping psychiatric disease genetic predisposition. Our analyses further highlight the importance of joint tissue approaches as 76% of the genes were detected only in difficult-to-acquire tissues.

DOI: 10.1038/s41588-019-0409-8

Source: https://www.nature.com/articles/s41588-019-0409-8