Genetic predisposition between coronavirus disease 2019 and rheumatic diseases: A 2‐sample Mendelian randomization study

Abstract

AbstractObjectiveThe causalities between the coronavirus disease 2019 (COVID‐19) and the risk of rheumatic diseases remain unclear. The purpose of this study was to investigate the causal effect of COVID‐19 on rheumatic disease occurrence.MethodsSingle nucleotide polymorphisms (SNPs), acquired from published genome‐wide association studies, were used to perform 2‐sample Mendelian randomization (MR) on cases diagnosed with COVID‐19 (n = 13 464), rheumatic diseases (n = 444 199), juvenile idiopathic arthritis (JIA, n = 15 872), gout (n = 69  374), systemic lupus erythematosus (SLE, n = 3094), ankylosing spondylitis (n = 75 130), primary biliary cholangitis (PBC, n = 11 375) and primary Sjögren's syndrome (n = 95 046). Three MR methods were used in the analysis based on different heterogeneity and pleiotropy using the Bonferroni correction.ResultsThe results revealed a causality between COVID‐19 and rheumatic diseases with an odds ratio (OR) of 1.010 (95% confidence interval [CI], 1.006–1.013; P = .014). In addition, we observed that COVID‐19 was causally associated with an increased risk of JIA (OR 1.517; 95%CI, 1.144–2.011; P = .004), PBC (OR 1.370; 95%CI, 1.149–1.635; P = .005), but a decreased risk of SLE (OR 0.732; 95%CI, 0.590–0.908; P = .004). Using MR, 8 SNPs were identified to associate with COVID‐19 and recognized as significant variables. None of them were previously reported in any other diseases.ConclusionsThis is the first study to use MR to explore the impact of COVID‐19 on rheumatic diseases. From a genetic perspective, we found that COVID‐19 could increase the risk of rheumatic diseases, such as PBC and JIA, but decrease that of SLE, thereby suggesting a potential surge in the disease burden of PBC and JIA following the COVID‐19 pandemic.