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

Int J Rheum Dis. 2023 Apr;26(4):710-717. doi: 10.1111/1756-185X.14624. Epub 2023 Mar 8.

Abstract

Objective: The 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.

Methods: Single 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.

Results: The 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.

Conclusions: This 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.

Keywords: Mendelian randomization; coronavirus disease 2019; juvenile idiopathic arthritis; primary biliary cholangitis; systemic lupus erythematosus.

MeSH terms

  • COVID-19* / complications
  • COVID-19* / epidemiology
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Lupus Erythematosus, Systemic* / diagnosis
  • Lupus Erythematosus, Systemic* / epidemiology
  • Lupus Erythematosus, Systemic* / genetics
  • Mendelian Randomization Analysis
  • Pandemics
  • Polymorphism, Single Nucleotide
  • Rheumatic Diseases* / diagnosis
  • Rheumatic Diseases* / epidemiology
  • Rheumatic Diseases* / genetics