1. Genome-wide Mendelian randomization and single-cell RNA sequencing analyses identify the causal effects of COVID-19 on 41 cytokines
- Author
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Chao Wang, Rui Yu, Sainan Zhang, Yue Zhao, Changlu Qi, Zijun Zhu, Xinyu Chen, Jianxing Bi, Peigang Xu, Liang Cheng, and Xue Zhang
- Subjects
Sequence Analysis, RNA ,Genetics ,Humans ,Cytokines ,COVID-19 ,General Medicine ,Mendelian Randomization Analysis ,Molecular Biology ,Biochemistry ,Polymorphism, Single Nucleotide ,Genome-Wide Association Study - Abstract
The elevated levels of inflammatory cytokines have attracted much attention during the treatment of COVID-19 patients. The conclusions of current observational studies are often controversial in terms of the causal effects of COVID-19 on various cytokines because of the confounding factors involving underlying diseases. To resolve this problem, we conducted a Mendelian randomization analysis by integrating the GWAS data of COVID-19 and 41 cytokines. As a result, the levels of 2 cytokines were identified to be promoted by COVID-19 and had unsignificant pleiotropy. In comparison, the levels of 10 cytokines were found to be inhibited and had unsignificant pleiotropy. Among down-regulated cytokines, CCL2, CCL3 and CCL7 were members of CC chemokine family. We then explored the potential molecular mechanism for a significant causal association at a single cell resolution based on single-cell RNA data, and discovered the suppression of CCL3 and the inhibition of CCL3-CCR1 interaction in classical monocytes (CMs) of COVID-19 patients. Our findings may indicate that the capability of COVID-19 in decreasing the chemotaxis of lymphocytes by inhibiting the CCL3-CCR1 interaction in CMs.
- Published
- 2022