Immune-mediated inflammatory diseases and risk of venous thromboembolism: A Mendelian randomization study

Abstract

IntroductionImmune-mediated inflammatory diseases (IMIDs) have been associated with an increased risk of venous thromboembolism (VTE) in multiple observational studies. However, a direct causally relation between IMIDs and VTE remains unclear to date. Here, we used Mendelian randomization (MR) analysis to investigate causal associations between IMIDs and VTE.MethodsWe collected genetic data from published genome-wide association studies (GWAS) for six common IMIDs, specifically inflammatory bowel disease (IBD), Crohn’s disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriasis (PSO), and systemic lupus erythematosus (SLE); and summary-level data for VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) from the FinnGen database. Two-sample MR analysis using inverse variance weighting (IVW) was performed to identify causal associations between IMIDs and VTE/DVT/PE, and sensitivity analyses were implemented for robustness.ResultsIVW analysis showed a causal relationship between genetically predicted UC (one type of IBD) and the risk of VTE (OR = 1.043, 95% CI: 1.013-1.073, p = 0.004) and DVT (OR = 1.088, 95% CI: 1.043-1.136, p < 0.001), but we found no evidence of causality between UC and PE (OR = 1.029, 95% CI: 0.986-1.074, p = 0.19). In addition, no associations were observed between total IBD, CD, RA, SLE, or PSO and VTE/DVT/PE. Sensitivity analysis found no evidence for horizontal pleiotropy.ConclusionThis MR study provides new genetic evidence for the causal relationship between IMIDs and the risk of VTE. Our findings highlight the importance of active intervention and monitoring to mitigate VTE risk in patients with IBD, in particular those presenting with UC.

Causal associations between autoimmune diseases and sarcopenia-related traits: a bi-directional Mendelian randomization study

“…The GWAS statistics for RA (5,201 cases and 45,732 controls) and PSO (5,314 cases and 457,619 controls) of European descent were obtained from the UK Biobank ( http://www.nealelab.is/uk-biobank/ ) ( Ma et al, 2022 ). The GWAS statistics for SLE (5,201 cases and 9,066 controls) of European descent were derived from the study by Lv et al (2022) . The GWAS statistics for MS (47,429 cases and 68,374 controls) of European descent were acquired from the International MS Genetics Consortium ( IMSGC, 2019 ).…”

Immune-mediated inflammatory diseases and periodontal disease: a bidirectional two-sample mendelian randomization study

“…IMID is an encompassing designation for a group of illnesses characterized by a similar inflammatory pathway and is defined by an immune system malfunction that can induce chronic inflammation within any organ in the body [ 9 , 10 ]. IMID includes Systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and ulcerative colitis (UC), among others, all manifesting a diverse set of clinical symptoms.…”

Causality between Atrial Fibrillation and Venous Thromboembolism: A Bidirectional Two-Sample Mendelian Randomization Study

“…Large-scale Genome-Wide Association Studies (GWAS) on circulatory diseases have made it possible to investigate the relationships between related diseases through MR analysis. As discovered from a study by Lv et al [6] , there was a causality between Ulcerative Colitis (UC) and VTE. Furthermore, Hu et al [7] and colleagues revealed no substantial causal relationship between type 1/type 2 diabetes and VTE risk, even after adjusting for possible confounding factors.…”