Disentangling the common genetic architecture and causality of rheumatoid arthritis and systemic lupus erythematosus with COVID‐19 outcomes: Genome‐wide cross trait analysis and bidirectional Mendelian randomization study
Open Access
- 16 February 2023
- journal article
- research article
- Published by Wiley in Journal of Medical Virology
- Vol. 95 (2), e28570
- https://doi.org/10.1002/jmv.28570
Abstract
Coronavirus Disease (COVID-19) may cause a dysregulation of the immune system and has complex relationships with multiple autoimmune diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, little is known about their common genetic architecture. Using the latest data from COVID-19 host genetics consortium and consortia on RA and SLE, we conducted a genome-wide cross-trait analysis to examine the shared genetic etiology between COVID-19 and RA/SLE and evaluated their causal associations using bidirectional Mendelian randomization (MR). The cross-trait meta-analysis identified 23, 28, and 10 shared genetic loci for severe COVID-19, COVID-19 hospitalization, and SARS-CoV-2 infection with RA, and 14, 17, and 7 shared loci with SLE, respectively. Co-localization analysis identified five causal variants in TYK2, IKZF3, PSORS1C1, and COG6 for COVID-19 with RA, and four in CRHR1, FUT2, and NXPE3 for COVID-19 with SLE, involved in immune function, angiogenesis and coagulation. Bidirectional MR analysis suggested RA is associated with a higher risk of COVID-19 hospitalization, and COVID-19 is not related to RA or SLE. Our novel findings improved the understanding of the genetic etiology shared by COVID-19, RA and SLE, and suggested an increased risk of COVID-19 hospitalization in people with higher genetic liability to RA.This publication has 50 references indexed in Scilit:
- Genetic and epigenetic fine mapping of causal autoimmune disease variantsNature, 2014
- Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary StatisticsPLoS Genetics, 2014
- Corticotropin-releasing Hormone and Its Biological Diversity toward AngiogenesisIntestinal Research, 2014
- Genetics of rheumatoid arthritis contributes to biology and drug discoveryNature, 2013
- WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013Nucleic Acids Research, 2013
- Genomic inflation factors under polygenic inheritanceEuropean Journal of Human Genetics, 2011
- Association of Systemic Lupus Erythematosus withC8orf13–BLKandITGAM–ITGAXThe New England Journal of Medicine, 2008
- Mendelian randomization: Using genes as instruments for making causal inferences in epidemiologyStatistics in Medicine, 2008
- MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibilityRheumatology, 2007
- ADAM15 is an adhesion receptor for platelet GPIIb-IIIa and induces platelet activationThrombosis and Haemostasis, 2005