![]() ![]() Over the past decade, genome-wide association studies (GWAS) have proved to be a useful tool for uncovering new infectious disease susceptibility loci, identifying loci associated with pathogen clearance or persistence and providing supporting evidence for the role of certain host factors implicated in disease progression and severity 6, 7. 4) and the sickle-cell-causing mutation in the HBB gene offering protection against the malaria-causing Plasmodium falciparum 5. Notable examples include the protective effects of the CCR5Δ32 mutation on infection with the human immunodeficiency virus type 1 (ref. Genetics plays a role in host susceptibility to infection and disease pathogenesis in humans 3. Much less is known about the genetic basis of COVID-19 risk, both in terms of susceptibility to infection and severity of outcomes after infection. It has been well documented that several host factors are correlated with disease progression, with primary risk factors including sex, age, ancestry and the presence of underlying medical conditions 2. Since the emergence of the disease, it has become clear that the course of the disease can vary considerably between individuals 1, with some experiencing mild or nonexistent symptoms and others experiencing severe outcomes, including hospitalization or even death. The COVID-19 pandemic has caused unprecedented disruption to modern societies throughout the world. 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. ![]() Hospitalization risk factors include advancing age, male sex, obesity, lower socioeconomic status, non-European ancestry and preexisting cardiometabolic conditions. 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. 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. COVID-19 presents with a wide range of severity, from asymptomatic in some individuals to fatal in others. ![]()
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