Department of Psychiatry, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Medical Laboratory Center, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Can J Psychiatry. 2020 Dec;65(12):874-884. doi: 10.1177/0706743720940547. Epub 2020 Jul 10.
Previous studies have inferred that there is a strong genetic component in insomnia. However, the etiology of insomnia is still unclear. This study systematically analyzed multiple genome-wide association study (GWAS) data sets with core human pathways and functional networks to detect potential gene pathways and networks associated with insomnia.
We used a novel method, multitrait analysis of genome-wide association studies (MTAG), to combine 3 large GWASs of insomnia symptoms/complaints and sleep duration. The i-Gsea4GwasV2 and Reactome FI programs were used to analyze data from the result of MTAG analysis and the nominally significant pathways, respectively.
Through analyzing data sets using the MTAG program, our sample size increased from 113,006 subjects to 163,188 subjects. A total of 17 of 1,816 Reactome pathways were identified and showed to be associated with insomnia. We further revealed 11 interconnected functional and topologically interacting clusters (Clusters 0 to 10) that were associated with insomnia. Based on the brain transcriptome data, it was found that the genes in Cluster 4 were enriched for the transcriptional coexpression profile in the prenatal dorsolateral prefrontal cortex ( = 7 × 10), inferolateral temporal cortex ( = 0.02), medial prefrontal cortex ( < 1 × 10), and amygdala ( < 1 × 10), and detected and as core nodes in these 4 brain regions.
The findings provided new genes, pathways, and brain regions to understand the pathology of insomnia.
先前的研究推断失眠存在强烈的遗传成分。然而，失眠的病因仍不清楚。本研究系统地分析了多个包含核心人类途径和功能网络的全基因组关联研究 (GWAS) 数据集，以检测与失眠相关的潜在基因途径和网络。
我们使用一种新的方法，即全基因组关联研究的多性状分析 (MTAG)，将 3 项关于失眠症状/抱怨和睡眠时间的大型 GWAS 进行了组合。使用 i-Gsea4GwasV2 和 Reactome FI 程序分别分析 MTAG 分析结果和名义上显著途径的数据。
通过使用 MTAG 程序分析数据集，我们的样本量从 113006 名受试者增加到 163188 名受试者。在 1816 个 Reactome 途径中，有 17 个被确定与失眠相关。我们进一步揭示了 11 个相互连接的功能和拓扑相互作用的聚类（Cluster 0 到 10），这些聚类与失眠有关。基于大脑转录组数据，发现 Cluster 4 中的基因在产前背外侧前额皮质（ = 7×10）、外侧颞叶皮质（ = 0.02）、内侧前额皮质（ < 1×10）和杏仁核（ < 1×10）中存在转录共表达谱的富集，并且在这 4 个大脑区域中检测到和作为核心节点。
这些发现为理解失眠的病理提供了新的基因、途径和大脑区域。
