Trans-ancestry analysis reveals genetic and nongenetic associations with COVID-19 susceptibility and severity

COVID-19 presents with a wide range of severity, from asymptomatic in some individuals to fatal in others. Based on a study of 1,051,032 23andMe research participants, we report genetic and nongenetic associations with testing positive for SARS-CoV-2, respiratory symptoms and hospitalization. Using trans-ancestry genome-wide association studies, we identified a strong association between blood type and COVID-19 diagnosis, as well as a gene-rich locus on chromosome 3p21.31 that is more strongly associated with outcome severity. Hospitalization risk factors include advancing age, male sex, obesity, lower socioeconomic status, non-European ancestry and preexisting cardiometabolic conditions. While non-European ancestry was a significant risk factor for hospitalization after adjusting for sociodemographics and preexisting health conditions, we did not find evidence that these two primary genetic associations explain risk differences between populations for severe COVID-19 outcomes. A study of more than one million 23andMe research participants identifies genetic and nongenetic associations with COVID-19 susceptibility and severity.