A genome-wide association study of COVID-19 related hospitalization in Spain reveals genetic disparities among sexes

Abstract We describe the results of the Spanish Coalition to Unlock Research on Host Genetics on COVID-19 (SCOURGE). In sex-disaggregated genome-wide studies of COVID-19 hospitalization, we found two known loci associated among males ( SLC6A20 - LZTFL1 and IFNAR2 ), and a novel one among females ( TLE1 ). Meta-analyses with independent studies revealed two novel associations ( AQP3 and ARHGAP33 ) and replicated ELF5 . A genetic risk score predicted COVID-19 severity, especially among younger males. We found less SNP-heritability and larger heritability differences by age (<60/≥60 years) among males than females. Inbreeding depression was associated with COVID-19 hospitalization and severity, and the effect was stronger among older males.