Abstract
Observational studies have reported an association between lipoprotein(a) (Lp(a)) and immune-mediated inflammatory diseases (IMIDs). This study used Mendelian Randomization (MR) and multivariable MR (MVMR) to explore the causal relationship between lipoprotein(a) [Lp(a)] and immune-mediated inflammatory diseases (IMIDs). We performed a bidirectional two-sample mendelian randomization analyses based on genome-wide association study (GWAS) summary statistics of Lp(a) and nine IMIDs, specifically celiac disease (CeD), Crohn's disease (CD), ulcerative colitis (UC), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis (Pso), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), and summary-level data for lipid traits. Furthermore, we performed MVMR to examine the independence of relationship between Lp(a) and IMIDs after controlling other lipid traits, namely high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). We didn't observe a causal association between Lp(a) and the risk of IMIDs in univariable and multivariable MR analysis, challenging previous observational studies. However, genetically predicted lipid traits HDL-C was associated with increased risk of Type 1 diabetes (T1D). The identification of potential mechanisms underlying the observed associations in observational studies necessitates further investigation.