An integrated strategy to identify COVID‐19 causal genes and characteristics represented by LRRC37A2

Author:

Zhu Zijun1,Chen Xinyu1,Wang Chao1,Zhang Sainan1,Yu Rui1,Xie Yubin23ORCID,Yuan Shuofeng23ORCID,Cheng Liang14,Shi Lei4,Zhang Xue45

Affiliation:

1. College of Bioinformatics Science and Technology Harbin Medical University Harbin Heilongjiang China

2. Department of Microbiology, Li Ka Shing Faculty of Medicine The University of Hong Kong Pokfulam Hong Kong SAR China

3. State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine The University of Hong Kong Pokfulam Hong Kong SAR China

4. NHC Key Laboratory of Molecular Probe and Targeted Diagnosis and Therapy Harbin Medical University Harbin Heilongjiang China

5. 3McKusick‐Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China

Abstract

AbstractGenome‐wide association study (GWAS) could identify host genetic factors associated with coronavirus disease 2019 (COVID‐19). The genes or functional DNA elements through which genetic factors affect COVID‐19 remain uncharted. The expression quantitative trait locus (eQTL) provides a path to assess the correlation between genetic variations and gene expression. Here, we firstly annotated GWAS data to describe genetic effects, obtaining genome‐wide mapped genes. Subsequently, the genetic mechanisms and characteristics of COVID‐19 were investigated by an integrated strategy that included three GWAS‐eQTL analysis approaches. It was found that 20 genes were significantly associated with immunity and neurological disorders, including prior and novel genes such as OAS3 and LRRC37A2. The findings were then replicated in single‐cell datasets to explore the cell‐specific expression of causal genes. Furthermore, associations between COVID‐19 and neurological disorders were assessed as a causal relationship. Finally, the effects of causal protein‐coding genes of COVID‐19 were discussed using cell experiments. The results revealed some novel COVID‐19‐related genes to emphasize disease characteristics, offering a broader insight into the genetic architecture underlying the pathophysiology of COVID‐19.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

Infectious Diseases,Virology

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