Effect of autoimmune diseases on aplastic anemia: a bidirectional two-sample Mendelian randomization study

Numerous observational research avenues have identified a possible correlation between aplastic anemia and autoimmune diseases, rooted in analogous dysfunctional immune responses. Nevertheless, causal link between autoimmune diseases and aplastic anemia remains elusive. The study aims to investigate the causal association of autoimmune diseases and aplastic anemia.

This study leveraged summary data from genome-wide association studies pertaining to six prevalent autoimmune diseases: ulcerative colitis, Crohn's disease, systemic lupus erythematosus, rheumatoid arthritis, celiac disease, and type 1 diabetes mellitus, procured from expansive, public genome-wide association studies meta-analysis databases. Aplastic anemia - related genetic information was extracted from the UK Biobank. Utilizing single nucleotide polymorphisms as genetic instruments - meeting criteria P < 5 × 10^-8 and linkage disequilibrium [LD] r² < 0.001 - the study employed Cochran's Q test, the MR-Egger intercept test, and leave-one-out analysis to gauge the sensitivity concerning the impact of autoimmune diseases on aplastic anemia.

The findings underscore a definitive causal relationship between systemic lupus erythematosus and aplastic anemia, as evidenced by the statistics (OR_IVW = 1.193, 95% CI 1.013-1.404, P = 0.035). Duplicate SLE GWAS from the FinnGen database demonstrated that patients with SLE are more susceptible to AA (OR_IVW = 1.193, 95% CI 1.013-1.404, P = 0.035). Additionally, the Mendelian randomization analysis reported no evidence of horizontal or directional pleiotropy.

In summary, the study suggests that systemic lupus erythematosus could serve as a potential risk factor contributing to the onset of aplastic anemia. To substantiate this hypothesis, ensuing studies encompassing larger sample sizes are warranted.