Identification of COVID-19 susceptibility genes by Mendelian randomization.

ObjectiveWe applied Mendelian Randomization (MR) to investigate potential genetic targets involved in the pathogenesis of COVID-19, aiming to identify causal factors that may contribute to disease susceptibility and severity.MethodsWe aggregated multi-omics quantitative trait loci data and explored the pathogenic targets of COVID-19 using summary data-based Mendelian randomization, colocalization, and MR.ResultsWe identified Latent transforming growth factor beta binding protein 2 (LTBP2) and α-1,3-N-acetylgalactosaminyltransferase (ABO) as primary targets for the risk of severe COVID-19. Elevated levels of LTBP2 (odds ratio (OR): 0.53, 95% CI: 0.39-0.70) were associated with reduced risk of severe COVID-19, while ABO (OR: 1.09, 95% CI: 1.06-1.11) were associated with increased risk of severe COVID-19. These effects were consistent with the expression of LTBP2 (OR: 0.58, 95% CI: 0.45-0.75) and the methylation of ABO (cg07241568: OR: 1.20, 95% CI: 1.14-1.26; cg24267699: OR: 1.11, 95% CI: 1.08-1.15) regarding the risk of severe COVID-19.ConclusionsWe have identified several potential genes related to COVID-19 risks, providing a basis for understanding the pathogenesis of COVID-19 and the development of candidate therapeutic drugs.