Genetic and Phenotypic Analysis of the Causal Relationship Between Aging and COVID-19

Overview

Journal Commun Med (Lond)

Publisher Nature Portfolio

Specialty General Medicine

Date 2022 May 23

PMID 35602207

Authors

Kejun Ying

Ranran Zhai

Timothy V Pyrkov

Anastasia V Shindyapina

Marco Mariotti

Peter O Fedichev

Xia Shen

Vadim N Gladyshev

Affiliations

Soon will be listed here.

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 ( = 9.7 × 10) and 0.46 ( = 3.3 × 10), 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.

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