Ying, KejunZhai, RanranPyrkov, Timothy V.Shindyapina, Anastasia V.Mariotti, Marco, 1984-Fedichev, Peter O.Shen, XiaGladyshev, Vadim N.2023-02-222023-02-222021-10-052730-664Xhttps://hdl.handle.net/2445/193936Background: Epidemiological studies revealed that the elderly and those with comorbidities are most affected by COVID-19, but it is important to investigate shared genetic mechanisms between COVID-19 risk and aging. Methods: We conducted a multi-instrument Mendelian Randomization analysis of multiple lifespan-related traits and COVID-19. Aging clock models were applied to the subjects with different COVID-19 conditions in the UK-Biobank cohort. We performed a bivariate genomic scan for age-related COVID-19 and Mendelian Randomization analysis of 389 immune cell traits to investigate their effect on lifespan and COVID-19 risk. Results: We show that the genetic variation that supports longer life is significantly associated with the lower risk of COVID-19 infection and hospitalization. The odds ratio is 0.31 (P = 9.7 × 10-6) and 0.46 (P = 3.3 × 10-4), respectively, per additional 10 years of life. We detect an association between biological age acceleration and future incidence and severity of COVID-19 infection. Genetic profiling of age-related COVID-19 infection indicates key contributions of Notch signaling and immune system development. We reveal a negative correlation between the effects of immune cell traits on lifespan and COVID-19 risk. We find that lower B-cell CD19 levels are indicative of an increased risk of COVID-19 and decreased life expectancy, which is further validated by COVID-19 clinical data. Conclusions: Our analysis suggests that the factors that accelerate aging lead to an increased COVID-19 risk and point to the importance of Notch signaling and B cells in both. Interventions that target these factors to reduce biological age may reduce the risk of COVID-19.15 p.application/pdfengcc-by (c) Ying, Kejun et al., 2021https://creativecommons.org/licenses/by/4.0/EnvellimentMalalties hereditàriesMalalties víriquesAgingGenetic diseasesVirus diseasesinfo:eu-repo/semantics/article7162732023-02-22info:eu-repo/semantics/openAccess