Mendelian randomization analysis does not reveal a causal influence between lipoprotein(A) and immune-mediated inflammatory diseases

Observational studies have reported an association between lipoprotein(a) (Lp(a)) and immune-mediated inflammatory diseases (IMIDs). Here, we aimed to explore causal relationship between Lp(a) and IMIDs by Mendelian randomization (MR) analysis. We performed a 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. We performed bidirectional and multivariable MR (MVMR) to examine the causal relationship of Lp(a) with IMIDs analysis and its independence after controlling other lipid traits, namely high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). The results indicated no causal relationship between Lp(a) and the risk of IMIDs in univariable and multivariable MR analysis (with all IVW P values > 0.05). In multivariable MR, genetically predicted HDL (OR _MVMR 0.80(0.68–0.95); P = 0.011) and TG (OR _MVMR 0.80(0.66–0.98); P = 0.033) linked to higher risk of type 1 diabetes, and genetically predicted LDL linked to higher risk of psoriasis (OR _MVMR 0.80(0.64–0.99); P = 0.045). This MR study found no evidence suggesting a causal link between lipoprotein(a) and IMIDs, which is contrary to the results of many observational studies. The identification of potential mechanisms underlying the observed associations in observational studies necessitates further investigation.