基于孟德尔随机化的焦谷氨酸与 COVID-19 因果关联研究。

Mendelian Randomization Study on Causal Association of Pyroglutamine with COVID-19.

机构信息

Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing, 100069, China.

出版信息

J Epidemiol Glob Health. 2022 Dec;12(4):541-547. doi: 10.1007/s44197-022-00073-1. Epub 2022 Oct 11.

DOI:10.1007/s44197-022-00073-1

PMID:36219338

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9552722/

Abstract

BACKGROUND

Glutamine family amino acids such as glutamate, pyroglutamate, and glutamine have been shown to play important roles in COVID-19. However, it is still unclear about the role of pyroglutamate in COVID-19. Thus, we use a two-sample Mendelian randomization (MR) study to identify the genetic causal link between blood pyroglutamine levels and COVID-19 risk.

METHODS

Pyroglutamine genetic instrumental variables (IVs) were chosen from the largest pyroglutamine-associated genome-wide association studies (GWAS). The largest COVID-19 GWAS dataset was employed to evaluate the causal link between blood pyroglutamine levels and COVID-19 risk using two-sample MR analysis.

RESULTS

We found no significant pleiotropy or heterogeneity of pyroglutamine-associated genetic IVs in COVID-19 GWAS. Interestingly, we found that as pyroglutamine genetically increased, the risk of COVID-19 decreased using inverse variance weighted (IVW) (Beta = - 0.644, p = 0.003; OR = 0.525, 95% CI [0.346-0.798]) and weighted median (Beta = - 0.609, p = 0.013; OR = 0.544, 95% CI [0.337-0.878]).

CONCLUSION

Our analysis suggests a causal link between genetically increased pyroglutamine and reduced risk of COVID-19. Thus, pyroglutamine may be a protective factor for patients with COVID-19.

摘要

背景

谷氨酸、焦谷氨酸和谷氨酰胺等谷氨酰胺家族氨基酸已被证明在 COVID-19 中发挥重要作用。然而，焦谷氨酸在 COVID-19 中的作用尚不清楚。因此，我们使用两样本孟德尔随机化（MR）研究来确定血液焦谷氨酸水平与 COVID-19 风险之间的遗传因果关系。

方法

从最大的焦谷氨酸相关全基因组关联研究（GWAS）中选择焦谷氨酸遗传工具变量（IVs）。使用最大的 COVID-19 GWAS 数据集，通过两样本 MR 分析评估血液焦谷氨酸水平与 COVID-19 风险之间的因果关系。

结果

我们发现与焦谷氨酸相关的遗传 IVs 在 COVID-19 GWAS 中没有明显的多效性或异质性。有趣的是，我们发现，随着焦谷氨酸的遗传增加，COVID-19 的风险降低，使用逆方差加权（IVW）（Beta=-0.644，p=0.003；OR=0.525，95%CI[0.346-0.798]）和加权中位数（Beta=-0.609，p=0.013；OR=0.544，95%CI[0.337-0.878]）。