Abstract 17794: Rheumatoid Arthritis is Associated With Hypertension in Mendelian Randomization Analysis

Abstract

Introduction: Epidemiologic studies have identified associations between multiple autoimmune diseases and hypertension. However, these studies can be biased by reverse causality and unmeasured confounding. Mendelian randomization (MR) is less susceptible to these biases and can provide insights into the etiological relationship between risk factors and outcomes. Question: Using MR, is there supportive evidence to suggest a causal relationship between autoimmune diseases and hypertension? Methods: Single nucleotide polymorphism (SNP)-based instrumental variables for type 1 diabetes mellitus, Crohn’s disease, ulcerative colitis, systemic lupus erythematosus, and rheumatoid arthritis were obtained from the NGHRI-EBI GWAS catalog of individuals of European ancestry using MR-Base, a database of instrumental variables derived from previously performed GWAS. The outcome was self-reported hypertension among UK Biobank participants with genome-wide genotyping of European ancestry. Two sample MR was performed using the TwoSampleMR R package, using the inverse variance weighted method with correction for linkage disequilibrium. Results: After correction for multiple comparisons using the false discovery rate, rheumatoid arthritis was associated with significantly higher odds of hypertension (beta= 0.0034, SE=0.0013, p=0.045). No significant associations were observed for type 1 diabetes mellitus (beta = 0.0046, SE=0.0023, p=0.103), Crohn’s disease (beta= 0.0023, SE= 0.0017, p= 0.267), ulcerative colitis (beta= -0.0014, SE=0.0011, p=0.267) and systemic lupus erythematosus (beta= -1.6x10 -8 , SE=0.0014, p=0.999). Sensitivity analysis using MR Egger revealed no significant confounding horizontal pleiotropy for the relationship between rheumatoid arthritis and hypertension (Egger-intercept= -0.0001, SE=0.0003, p=0.677). Conclusion: Using MR, a causal association was suggested between rheumatoid arthritis and hypertension. There was no evidence for an etiologic relationship observed with other autoimmune disease exposures tested. These findings suggest a role for rheumatoid arthritis in promoting hypertension development, which we theorize may be through enhanced immune activation.