The Role of Host Genetic Factors in Coronavirus Susceptibility: Review of Animal and Systematic Review of Human Literature

BackgroundThe recent SARS-CoV-2 pandemic raises many scientific and clinical questions. One set of questions involves host genetic factors that may affect disease susceptibility and pathogenesis. New work is emerging related to SARS-CoV-2; previous work on other coronaviruses in humans or other host species may be relevant. ObjectivesTo review existing literature on host genetic factors and their association with infection and disease with coronaviruses in humans and in other host species. MethodsWe conducted a systematic review of literature on host genetic factors in humans associated with coronavirus outcomes. We also reviewed studies of host genetic factors associated with coronavirus outcomes in non-human species. We categorized articles, summarized themes related to animal studies, and extracted data from human studies for analyses. ResultsWe identified 1,187 articles of potential relevance. Forty-five studies examined human host genetic factors related to coronavirus, of which 35 involved analysis of specific genes or loci; aside from one meta-analysis on respiratory infections, all were candidate-driven studies, typically investigating small numbers of research subjects and loci. Multiple significant loci were identified, including 16 related to susceptibility to coronavirus (of which 7 identified protective alleles), and 16 related to outcomes or clinical variables (of which 3 identified protective alleles). The types of cases and controls used varied considerably; four studies used traditional replication/validation cohorts. Of the other studies, 28 involved both human and non-human host genetic factors related to coronavirus, and 174 involved study of non-human (animal) host genetic factors related to coronavirus. Key findingsWe have outlined key genes and loci from animal and human host genetic studies that may bear investigation in the nascent host genetic factor studies of COVID-19. Previous human studies have been limited by relatively low numbers of eligible participants and limited availability of advanced genomic methods. These limitations may be less important to studies of SARS-CoV-2.