AncestryDNA COVID 19 Host Genetic Study Identifies Three Novel Loci

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][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. ### Competing Interest Statement The authors declare competing financial interests: authors affiliated with AncestryDNA are employed by Ancestry and may have equity in Ancestry. ### Funding Statement All work was supported and funded by AncestryDNA ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All data for this research project was from subjects who provided prior informed consent to participate in AncestryDNAs Human Diversity Project, as reviewed and approved by our external institutional review board, Advarra (formerly Quorum). All data was de-identified prior to use. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Additional supplementary data files may be shared with qualified researchers on a case by case basis. Please reach out to cball{at}ancestry.com. [1]: #ref-1