Fig. 2
Risk genes and pathways associated with hospitalized COVID-19 from meta-GWAS summary data. A Manhattan plot and quantile-quantile (QQ) plot of meta-GWAS analysis highlighting eight risk genetic loci for hospitalized COVID-19. The red horizontal line represents the genome-wide significance threshold of P < 5×10−8. The genomic inflation factor λ = 1.02. B Nine index SNPs within eight genomic loci associated with hospitalized COVID-19. The left panel shows the P value of each index SNP, and the right panel shows the odds ratio with 95% confidence interval. C Circus plot showing the results of the S-MultiXcan-based analysis. The inner ring demonstrates the 22 autosomal chromosomes (Chr1-22). In the outer ring, a circular symbol represents a specific gene and color marks the statistical significance of the gene for hospitalized COVID-19 (red marks FDR < 0.05, orange indicates 6.96×10−5 ≤ P < 0.001, light blue marks 0.001 ≤ P ≤ 0.05, and dark blue indicates P > 0.0). D PPI network of these 34 identified risk genes based on the STRING database (v11.0, https://string-db.org/). The orange ring represents druggable genes targeted by at least one known drug. E Network module constructed by using the Jaccard distance showing the connectivity of 10 significant pathways enriched by 34 risk genes. F Heatmap showing the results of hierarchical clustering analysis of 27 risk genes on COVID-19 severity. Seven risk genes did not express in dataset #1, and the expression level of each gene was scaled. G The proportion of highly expressed genes among 27 risk genes in normal controls and in the three phases of COVID-19 (mild, moderate, and severe patients). Using 10,000 times of permutation analysis to calculate the significance of the observation (permuted P = 0.023). H Plot showing an increase of the significantly enriched pathways in the network module with elevated COVID-19 severities. Orange color represents a significantly enriched pathway (FDR ≤ 0.05) and gray color represents a non-significantly enriched pathway (FDR > 0.05)