Genome-wide association study suggests that CPQ influences the Omicron variant COVID-19 severity

Abstract

Host genetic background has been indicated in the severity of coronavirus disease 2019 (COVID-19) with multiple genetic variants identified, either across or in specific populations. However, previous host genetic studies of COVID-19 were either pre-Omicron era or conducted on various mutants of SARS-CoV-2, and few were performed among non-European populations. To investigate the genetic variation contributing to the severity of infections with SARS-CoV-2 Omicron variant, we performed a genome-wide association study among 5,151 Chinese individuals newly infected with SARS-CoV-2 since January 2022 (269 severe cases and 4,882 mild cases). We identified a novel genomic locus on chromosome 8q22.1 (rs7817424, P-value = 4.60×10−8) in the CPQ gene that is involved in hydrolysis of circulating peptides. Gene mapping approach using colocalization of eQTL, pQTL and sQTL data and similarity-based gene prioritization suggested CPQ as the risk gene. Multiple analyses using single-cell RNA sequencing data, in combination with transcription factor binding motif analyses support a role of the CPQ gene in the manifestation of severe symptoms of the Omicron variant, which might be through involvement in the NF-κB pathway activation. Future confirmatory studies are warranted and may help identify mechanistic targets for therapeutic development.