Identification of biological correlates associated with respiratory failure in COVID-19

Coronavirus disease 2019 (COVID-19) is a global public health concern. Recently, a genome-wide association study (GWAS) was performed with participants recruited from Italy and Spain by an international consortium group.

Summary GWAS statistics for 1610 patients with COVID-19 respiratory failure and 2205 controls were downloaded. In the current study, we analyzed the summary statistics with the information of loci and p-values for 8,582,968 single-nucleotide polymorphisms (SNPs), using gene ontology analysis to determine the top biological processes implicated in respiratory failure in COVID-19 patients.

We considered the top 708 SNPs, using a p-value cutoff of 5 × 10^- 5, which were mapped to the nearest genes, leading to 144 unique genes. The list of genes was input into a curated database to conduct gene ontology and protein-protein interaction (PPI) analyses. The top ranked biological processes were wound healing, epithelial structure maintenance, muscle system processes, and cardiac-relevant biological processes with a false discovery rate < 0.05. In the PPI analysis, the largest connected network consisted of 8 genes. Through a literature search, 7 out of the 8 gene products were found to be implicated in both pulmonary and cardiac diseases.

Gene ontology and PPI analyses identified cardio-pulmonary processes that may partially explain the risk of respiratory failure in COVID-19 patients.