Figure 1

SARS-CoV-2 associated GWAS SNPs were assessed to ascertain loci functionality and identify putative mechanisms for comorbid and genetic predispositions for traits associated with SARS-CoV-2. (a) The Codes3D pipeline generates the index level set of target genes (Supplementary Fig. 1d) associated with the severe and hospitalised phenotypes. SNPs obtained from COVID-19 HGI⁴⁷ (Supplementary Table 1) were screened through tissue-specific Hi-C datasets^30,53,54,55 to identify cis (< 1 Mb), trans (> 1 Mb) and trans-interchromosomal SNP-gene interactions. eQTL effects were identified by testing the SNP-gene pairs against the GTEx database (version 8)²⁸. The resulting statistically significant (FDR ≤ 0.05) SARS-CoV-2-specific genes (spatial eQTL-gene pairs), from both the hospitalised and severe phenotypes were assessed for protein–protein interactions using the STRING⁵⁶ and PROPER-Seq³² databases. All genes were assessed using g:Profiler⁵⁷ to obtain gene ontology terms. (b) The protein–protein interaction network analysis pipeline has two parts: (1) all interacting protein partners from level 0 (CoDeS3D identified index level set of genes) to level 4 were identified by querying the STRING database with parameters of high confidence threshold score > 0.7; and (2) tissue-specific gene regulatory maps were queried to obtain all known eQTLs for each protein within the expanded network. The eQTLs were then tested for enrichment (hypergeometric test) within the GWAS Catalog (https://www.ebi.ac.uk/gwas/) to identify associated phenotypes.