Bidirectional mendelian randomization assessment of causality between lactate levels and multiple autoimmune diseases

Bidirectional two-sample Mendelian randomization (MR) was performed to provide genetic evidence for the causal association between multiple sclerosis (MS), type 1 diabetes(T1D), rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), Crohn's disease (CD), systemic lupus erythematosus (SLE), ulcerative colitis (UC) and lactate levels. Inverse variance weighted (IVW), weighted median estimator (WME), weighted mode, and MR-Egger regression were used to assess the potential causal links. Sensitivity analysis included Cochran's Q test for heterogeneity, Steiger test of directionality for directionality, MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out method. MR analysis utilized 510 SNPs associated with seven different kinds of autoimmune diseases and 11 SNPs associated with lactate levels as IVs. No significant genetic association between any autoimmune diseases and lactate levels was discovered by IVW. While IVW revealed no significant associations, exploratory analyses using WME and weighted mode methods identified nominal links between RA/IBD and lactate levels (RA: WME OR = 1.01, P = 0.010; weighted mode OR = 1.01, P = 0.008; IBD: weighted mode OR = 1.01, P = 0.042). These findings, though not surviving FDR correction, warrant further investigation. In reverse MR analysis, there was no significant association between lactate level exposure and any autoimmune disease outcomes. MR-Egger regression indicated potential horizontal pleiotropy in the RA-lactate analysis and Cochran's Q test suggest no absence of heterogeneity. Potential reverse causality in the analysis of SLE as outcomes and lactate levels as exposures was discovered by MR Steiger. Based on limited evidence, Our MR Analysis found a possible genetic causal association between RA and lactate level difference.