Causal relationship between autoimmune diseases and iron deficiency anemia: a two-sample mendelian randomization study.

Iron deficiency anemia (IDA) is a major contributor to global morbidity and disease burden. While observational studies have suggested associations between autoimmune diseases (ADs) and IDA, the causal nature of these relationships remains unclear. This study aimed to explore the potential causal effects of ADs on IDA. A bidirectional two-sample Mendelian randomization (MR) analysis was conducted using summary-level data from genome-wide association studies (GWAS). Genetic variants associated with exposures at genome-wide significance (P < 5 × 10⁻⁸) were selected as instrumental variables. Steiger filtering was applied to exclude SNPs explaining more variance in the outcome than in the exposure. Radial regression was used to detect outliers, and the inverse variance weighted (IVW) method served as the primary analytical approach. Sensitivity analyses were performed using MR-Egger regression, Cochran’s Q test, and the MR-PRESSO global test. IVW analysis revealed significantly increased risks of IDA associated with genetically predicted rheumatoid arthritis, inflammatory bowel disease, and ulcerative colitis after excluding variants in the MHC region. Suggestive associations were observed for ankylosing spondylitis, celiac disease, Crohn’s disease, and systemic lupus erythematosus, while the association with membranous nephropathy was no longer significant after MHC removal. This study provides evidence supporting potential causal relationships between several ADs and IDA, with the strongest evidence observed for rheumatoid arthritis, inflammatory bowel disease, and ulcerative colitis. Further investigations are warranted to elucidate the underlying biological mechanisms and to perform gender-specific and ancestry-stratified analyses.