Trans-ethnic analysis reveals genetic and non-genetic associations with COVID-19 susceptibility and severity

Shelton, J. F.; Shastri, A. J.; Ye, C.; Weldon, C. H.; Filshtein-Somnez, T.; Coker, D.; Symons, A.; Esparza-Gordillo, J.; The 23andMe COVID-19 Team,; Aslibekyan, S.; Auton, A.

COVID-19 presents with a wide range of severity, from asymptomatic in some individuals to fatal in others. Based on a study of over one million 23andMe research participants, we report genetic and non-genetic associations with testing positive for COVID-19, respiratory symptoms, and hospitalization. Risk factors for hospitalization include advancing age, male sex, elevated body mass index, lower socio-economic status, non-European ancestry, and pre-existing cardio-metabolic and respiratory conditions. Using trans-ethnic genome-wide association studies, we identify a strong association between blood type and COVID-19 diagnosis, as well as a gene-rich locus on chr3p21.31 that is more strongly associated with outcome severity. While non-European ancestry was found to be a significant risk factor for hospitalization after adjusting for socio-demographics and pre-existing health conditions, we did not find evidence that these two primary genetic associations explain differences between populations in terms of risk for severe COVID-19 outcomes.