AncestryDNA COVID-19 Host Genetic Study Identifies Three Novel Loci

Abstract Human infection with SARS-CoV-2, the causative agent of COVID-19, leads to a remarkably diverse spectrum of outcomes, ranging from asymptomatic to fatal. Recent reports suggest that both clinical and genetic risk factors may contribute to COVID-19 susceptibility and severity. To investigate genetic risk factors, we collected over 500,000 COVID-19 survey responses between April and May 2020 with accompanying genetic data from the AncestryDNA database. We conducted sex-stratified and meta-analyzed genome-wide association studies (GWAS) for COVID-19 susceptibility (positive nasopharyngeal swab test, n cases =2,407) and severity (hospitalization, n cases =250). The severity GWAS replicated associations with severe COVID-19 near ABO and SLC6A20 ( P <0.05). Furthermore, we identified three novel loci with P <5×10 −8 . The strongest association was near IVNS1ABP , a gene involved in influenza virus replication 1 , and was associated only in males. The other two novel loci harbor genes with established roles in viral replication or immunity: SRRM1 and the immunoglobulin lambda locus. We thus present new evidence that host genetic variation likely contributes to COVID-19 outcomes and demonstrate the value of large-scale, self-reported data as a mechanism to rapidly address a health crisis.