iScience . A Chinese host genetic study discovered IFNs and causality of laboratory traits on COVID-19 severity

[tetano]

iScience


. 2021 Sep 30;103186.
doi: 10.1016/j.isci.2021.103186. Online ahead of print.
A Chinese host genetic study discovered IFNs and causality of laboratory traits on COVID-19 severity


Huanhuan Zhu ¹ , Fang Zheng ² , Linxuan Li ^{1 3} , Yan Jin ⁴ , Yuxue Luo ^{1 5} , Zhen Li ⁶ , JingYu Zeng ^{1 7} , Ling Tang ⁶ , Zilong Li ¹ , Ningyu Xia ⁶ , Panhong Liu ^{1 3} , Dan Han ⁶ , Ying Shan ¹ , Xiaoying Zhu ⁶ , Siyang Liu ^{1 8} , Rong Xie ⁶ , Yilin Chen ⁶ , Wen Liu ⁶ , Longqi Liu ¹ , Xun Xu ^{1 9} , Jian Wang ^{1 10} , Huanming Yang ^{1 10} , Xia Shen ¹¹ , Xin Jin ^{1 5} , Fanjun Cheng ⁶



Affiliations

• PMID: 34608450
• PMCID: PMC8481128
• DOI: 10.1016/j.isci.2021.103186

Abstract

The COVID-19 pandemic has caused over 220 million infections and 4.5 million deaths worldwide. Current risk factor cannot fully explain the diversity in disease severity. Here, we present a comprehensive analysis of a broad range of patients' laboratory and clinical assessments to investigate the genetic contributions to COVID-19 severity. By performing GWAS analysis, we discovered several concrete associations for laboratory traits, and used Mendelian randomization (MR) analysis to further investigate the causality of traits on disease severity. Two causal traits, WBC counts and cholesterol levels, were identified based on MR study, and their functional genes are located at genes MHC complex and ApoE, respectively. Our gene-based and GSEA analysis revealed four interferon pathways, including type I interferon receptor binding and SARS coronavirus and innate immunity. We hope that our work will contribute to studying the genetic mechanisms of disease and serve as a useful reference for COVID-19 diagnosis and treatment. Keywords: COVID-19, Genome-wide association study, Mendelian randomization, GSEA analysis, MHC complex, ApoE gene, IFNs pathway.