Association Between COVID-19 and Neurological Diseases: Evidence from Large-Scale Mendelian Randomization Analysis and Single-Cell RNA Sequencing Analysis

作者全名："Huang, Lin; Wang, Yongheng; He, Yijie; Huang, Dongyu; Wen, Tong; Han, Zhijie"

作者地址："[Huang, Lin; Wang, Yongheng; He, Yijie; Huang, Dongyu; Wen, Tong; Han, Zhijie] Chongqing Med Univ, Sch Basic Med, Dept Bioinformat, Chongqing, Peoples R China; [Wang, Yongheng] Chongqing Med Univ, Int Res Lab Reprod & Dev, Chongqing, Peoples R China"

通信作者："Han, ZJ (通讯作者)，Chongqing Med Univ, Sch Basic Med, Dept Bioinformat, Chongqing, Peoples R China."

来源：MOLECULAR NEUROBIOLOGY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001154088900002

JCR分区：Q1

影响因子：5.1

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：COVID-19; Neurological diseases; Mendelian randomization; Single-cell RNA sequencing analysis

摘要："Observational studies have suggested that SARS-CoV-2 infection increases the risk of neurological diseases, but it remains unclear whether the association is causal. The present study aims to evaluate the causal relationships between SARS-CoV-2 infections and neurological diseases and analyzes the potential routes of SARS-CoV-2 entry at the cellular level. We performed Mendelian randomization (MR) analysis with CAUSE method to investigate causal relationship of SARS-CoV-2 infections with neurological diseases. Then, we conducted single-cell RNA sequencing (scRNA-seq) analysis to obtain evidence of potential neuroinvasion routes by measuring SARS-CoV-2 receptor expression in specific cell subtypes. Fast gene set enrichment analysis (fGSEA) was further performed to assess the pathogenesis of related diseases. The results showed that the COVID-19 is causally associated with manic (delta_elpd, - 0.1300, Z-score: - 2.4; P = 0.0082) and epilepsy (delta_elpd: - 2.20, Z-score: - 1.80; P = 0.038). However, no significant effects were observed for COVID-19 on other traits. Moreover, there are 23 cell subtypes identified through the scRNA-seq transcriptomics data of epilepsy, and SARS-CoV-2 receptor TTYH2 was found to be specifically expressed in oligodendrocyte and astrocyte cell subtypes. Furthermore, fGSEA analysis showed that the cell subtypes with receptor-specific expression was related to methylation of lysine 27 on histone H3 (H3K27ME3), neuronal system, aging brain, neurogenesis, and neuron projection. In summary, this study shows causal links between SARS-CoV-2 infections and neurological disorders such as epilepsy and manic, supported by MR and scRNA-seq analysis. These results should be considered in further studies and public health measures on COVID-19 and neurological diseases."

基金机构：the Science and Technology Research Program of Chongqing Municipal Education Commission; Supercomputer Center of Chongqing Medical University

基金资助正文："We thank the GWAS summary statistics provided by MR-Base platform. We are grateful that the scRNA-seq data for epilepsy studies are publicly available. We also thank the technical support of the Supercomputer Center of Chongqing Medical University for the numerical calculation of this study, and we thank all the investigators and participants who contributed to those studies."