小柯机器人

荷兰阿姆斯特丹自由大学Danielle Posthuma研究团队发现，失眠症的全基因组元分析将与代谢和精神病学途径有关的基因列为优先因素。相关论文于2022年7月14日在线发表在《自然—遗传学》杂志上。

研究人员表示，失眠是一种可遗传的、高度流行的睡眠障碍，目前没有足够的治疗方法。以前对130万受试者进行的全基因组关联研究确定了200多个相关位点。这种极端的多基因性表明还有更多的位点有待发现。目前的研究几乎将样本量增加了一倍，达到593,724个病例和1,771,286个对照，从而提高了统计能力，并确定了554个风险位点（包括364个新位点）。

为了利用这大量的基因位点，研究人员提出了一个新的策略，利用外部生物资源和跨风险位点的基因之间的功能相互作用来确定基因的优先次序。在所有3,898个从风险位点牵连出来的基因中，研究人员对289个进行了优先排序，并发现脑组织的表达特异性和突触信号功能和神经元分化的特定基因组的富集。结果表明，这种新的基因优先排序策略产生了关于失眠症潜在机制的具体假设，而这些假设会被传统方法所忽略。

附：英文原文

Title: Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways

Author: Watanabe, Kyoko, Jansen, Philip R., Savage, Jeanne E., Nandakumar, Priyanka, Wang, Xin, Hinds, David A., Gelernter, Joel, Levey, Daniel F., Polimanti, Renato, Stein, Murray B., Van Someren, Eus J. W., Smit, August B., Posthuma, Danielle

Issue&Volume: 2022-07-14

Abstract: Insomnia is a heritable, highly prevalent sleep disorder for which no sufficient treatment currently exists. Previous genome-wide association studies with up to 1.3million subjects identified over 200associated loci. This extreme polygenicity suggested that many more loci remain to be discovered. The current study almost doubled the sample size to 593,724cases and 1,771,286controls, thereby increasing statistical power, and identified 554risk loci (including 364novel loci). To capitalize on this large number of loci, we propose a novel strategy to prioritize genes using external biological resources and functional interactions between genes across risk loci. Of all 3,898genes naively implicated from the risk loci, we prioritize 289 and find brain-tissue expression specificity and enrichment in specific gene sets of synaptic signaling functions and neuronal differentiation. We show that this novel gene prioritization strategy yields specific hypotheses on underlying mechanisms of insomnia that would have been missed by traditional approaches.

DOI: 10.1038/s41588-022-01124-w

Source: https://www.nature.com/articles/s41588-022-01124-w

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex