The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a wide spectrum of clinical phenotypes ranging from asymptomatic to symptomatic with mild or moderate presentation and severe disease. COVID-19 susceptibility, severity and recovery have demonstrated high variability worldwide. Variances in the host genetic architecture may underlie the inter-individual and population-scale differences in COVID-19 presentation. We performed a genome-wide association analysis employing the genotyping data from AncestryDNA for COVID-19 patients of European descent and used asymptomatic subjects as the control group. We identified 621 genetic variants that were significantly distinct between asymptomatic and acutely symptomatic COVID-19 patients (multiple-testing corrected p -value < 0.001). These variants were found to be associated with pathways governing host immunity, such as interferon, interleukin and cytokine signalling, and known COVID-19 comorbidities, such as obesity and cholesterol metabolism. Further, our ancestry analysis revealed that the asymptomatic COVID-19 patients possess discernibly higher proportions of the Ancestral North Eurasian (ANE) and Eastern Hunter-Gatherer (EHG) ancestry, which was introduced to Europe through Bell Beaker culture (Yamnaya related) and lower fractions of Western Hunter-Gatherer (WHG) ancestry, while severely symptomatic patients have higher fractions of WHG and lower ANE/EHG ancestral components, thereby delineating the likely ancestral differences between the two groups.
【저자키워드】 ancestral genetic variation in COVID-19 patients, genome-wide association study for COVID-19 patients, asymptomatic COVID-19 patients as control, ANE and WHG ancestries in COVID-19, multiple regression with ancestral fractions, 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, coronavirus, Europe, obesity, severity, variant, Comorbidities, interferon, cytokine, metabolism, Asymptomatic, symptomatic, Patient, pathway, Mild, cholesterol, Genetic variant, genotyping, moderate, COVID-19 susceptibility, clinical phenotype, Analysis, severe disease, COVID-19 patient, Asymptomatic COVID-19, acute respiratory syndrome, control group, two groups, components, host immunity, P -value, variance, fraction, North, high variability, genetic architecture, genome-wide association, Host, European, Bell, performed, caused, significantly, proportion, characterized, introduced, demonstrated, underlie, asymptomatic subject, Beaker culture, inter-individual, multiple-testing, symptomatic patient, 【제목키워드】 COVID-19, clinical, manifestation, individual, descent, European,