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http://hdl.handle.net/2445/193936
Title: | Genetic and phenotypic analysis of the causal relationship between aging and COVID-19 |
Author: | Ying, Kejun Zhai, Ranran Pyrkov, Timothy V. Shindyapina, Anastasia V. Mariotti, Marco, 1984- Fedichev, Peter O. Shen, Xia Gladyshev, Vadim N. |
Keywords: | Envelliment Malalties hereditàries Malalties víriques Aging Genetic diseases Virus diseases |
Issue Date: | 5-Oct-2021 |
Publisher: | Nature Publishing Group |
Abstract: | Background: 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s43856-021-00033-z |
It is part of: | Communications medicine, 2021, vol. 1, p. 1-15 |
URI: | http://hdl.handle.net/2445/193936 |
Related resource: | https://doi.org/10.1038/s43856-021-00033-z |
ISSN: | 2730-664X |
Appears in Collections: | Articles publicats en revistes (Genètica, Microbiologia i Estadística) |
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