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新型冠状病毒肺炎(COVID-19)与重症肌无力(MG)的关联:一项遗传关联和孟德尔随机化研究。

Association between COVID-19 and myasthenia gravis (MG): A genetic correlation and Mendelian randomization study.

机构信息

Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Brain Behav. 2023 Nov;13(11):e3239. doi: 10.1002/brb3.3239. Epub 2023 Aug 28.

DOI:10.1002/brb3.3239
PMID:37638499
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10636397/
Abstract

BACKGROUND

Observational studies have suggested an association between coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG). Here, we aimed to estimate the genetic correlation and causal relationship between COVID-19 susceptibility, hospitalization, severity, and MG phenotypes using linkage disequilibrium score regression (LDSC) and Mendelian randomization (MR) approach.

METHODS

Summary statistics of COVID-19 susceptibility, hospitalization, and severity were used as instrumental variables for exposure traits. Large-scale genome-wide association study (GWAS) data for MG were used as outcome traits. The inverse variance weighted approach was used for the main MR analysis, complemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Sensitivity analysis was implemented using Cochran's Q test, MR-PRESSO method, and MR-Egger intercept test.

RESULTS

LDSC analysis did not reveal any genetic correlation among COVID-19 susceptibility, hospitalization, severity, and MG phenotypes, including MG, early-onset MG, and late-onset MG (p > .05). Our MR analysis did not provide evidence supporting a causal effect of COVID-19 susceptibility, hospitalization, or severity on MG phenotypes (p > .05). Extensive sensitivity analysis strengthened the robustness and consistency of the MR estimates.

CONCLUSION

Our study did not find evidence of a genetic correlation or causal relationship among COVID-19 susceptibility, hospitalization, severity, and MG. Future studies with more GWAS data are needed to evaluate the association between COVID-19 phenotypes and MG and its subgroups.

摘要

背景

观察性研究表明,2019 年冠状病毒病(COVID-19)与重症肌无力(MG)之间存在关联。在这里,我们旨在使用连锁不平衡得分回归(LDSC)和孟德尔随机化(MR)方法估计 COVID-19 易感性、住院、严重程度和 MG 表型之间的遗传相关性和因果关系。

方法

使用 COVID-19 易感性、住院和严重程度的汇总统计数据作为暴露特征的工具变量。使用大规模全基因组关联研究(GWAS)数据作为 MG 的结果特征。主要 MR 分析采用逆方差加权方法,辅以 MR-Egger、加权中位数、简单模式和加权模式方法。使用 Cochran's Q 检验、MR-PRESSO 方法和 MR-Egger 截距检验进行敏感性分析。

结果

LDSC 分析未发现 COVID-19 易感性、住院和严重程度与 MG 表型(包括 MG、早发性 MG 和晚发性 MG)之间存在任何遗传相关性(p>.05)。我们的 MR 分析没有提供证据支持 COVID-19 易感性、住院或严重程度对 MG 表型的因果作用(p>.05)。广泛的敏感性分析增强了 MR 估计的稳健性和一致性。

结论

我们的研究没有发现 COVID-19 易感性、住院、严重程度和 MG 之间存在遗传相关性或因果关系的证据。需要更多的 GWAS 数据来评估 COVID-19 表型与 MG 及其亚组之间的关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d691/10636397/12ad471ac61a/BRB3-13-e3239-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d691/10636397/12ad471ac61a/BRB3-13-e3239-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d691/10636397/12ad471ac61a/BRB3-13-e3239-g002.jpg

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