Genetics
Mendelian randomisation finds no causal link between Lp(a) and nine immune-mediated inflammatory diseases (Sci Rep 2025)
Original title: Mendelian randomization analysis does not support a causal influence between lipoprotein(A) and immune-mediated inflammatory diseases
Using bidirectional two-sample and multivariable Mendelian randomisation on genome-wide association study summary statistics, the authors tested whether Lp(a) causally influences nine immune-mediated inflammatory diseases: celiac disease, Crohn's disease, ulcerative colitis, inflammatory bowel disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. No causal association between Lp(a) and any of the nine conditions was found in either univariable or multivariable analysis after adjusting for HDL-C, LDL-C and triglycerides, challenging prior observational reports of a link. Genetically predicted HDL-C, but not Lp(a), was associated with increased risk of type 1 diabetes. The negative result argues that observed Lp(a)-inflammatory disease associations in cohort studies likely reflect confounding rather than causation.
Original 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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.