Genomic and ancestral variation underlies the severity of COVID-۱۹ clinical manifestation in individuals of European descent

Backgrounds: The coronavirus disease (COVID-۱۹) caused by the novel severe acuterespiratory syndrome coronavirus ۲ (SARS-CoV-۲) is characterized by a wide spectrum ofclinical phenotypes ranging in acuteness from asymptomatic, symptomatic with mild ormoderate manifestation and severe involving pneumonia and respiratory distress.Materials and Methods: We performed a genome-wide association study (GWAS) employingthe genotyping data from AncestryDNA COVID-۱۹ host genetic study that included COVID-۱۹positive patients and healthy individuals who had tested negative for SARS-CoV-۲ infection atthe time of recruitment. Further, we employed the asymptomatic individuals as controls insteadof healthy individuals. GWAS was performed in PLINK v۱.۹ with and without age correction.The genomic ancestry of COVID-۱۹ patients was determined using ADMIXTURE v۱.۳ andqpAdm algorithm implemented in AdmixTools v۵.۱.Results: Our data revealed striking genomic differences between COVID-۱۹ asymptomatic andseverely symptomatic individuals. We identified ۶۲۱ genetic variants that were significantlydistinct (Multiple-testing corrected P<۰.۰۰۱) between asymptomatic and acutely symptomaticCOVID-۱۹ patients. These variants were found to be associated with pathways governing hostimmunity, such as innate and adaptive immune system, interferon signaling, interleukinsignaling, and antigen processing by MHC, cytokine signaling and known COVID-۱۹comorbidities, such as obesity, cholesterol metabolism and smoking. Our ancestry analysis,employing qpAdm algorithm revealed that asymptomatic individuals possess discernibly higherproportions of Ancestral North Eurasian (ANE) and Eastern Hunter Gatherer (EHG) ancestryand lower fractions of Western Hunter Gatherer (WHG) ancestry, while severely symptomaticpatients have higher fractions of WHG and lower ANE/EHG ancestral components, therebydelineating the likely ancestral differences between the two groups.Conclusion: Overall, our studies suggest that asymptomatic individuals derived significantlylarger proportions of their ancestry from ANEs/EHGs, which was introduced to Europe throughBell Beaker culture (Yamnaya related), a smaller proportion of indigenous WHG ancestryfractions, while severely symptomatic COVID-۱۹ patients possess significantly larger fractionsof WHG related ancestry.

کلیدواژه ها:

COVID-۱۹ ، AncestryDNA ، GWAS