Mendelian Randomization Analysis Reveals the Causal Relationships Between Autoimmune Diseases and Idiopathic Thrombocytopenic Purpura and the Mediating Role of Immune Cells.

Abstract

Background: Idiopathic thrombocytopenic purpura (ITP) is related to multiple autoimmune diseases clinically, yet the causal relationship remains unclear. This study employed Mendelian randomization (MR) to explore the genetic causal relationship between autoimmune diseases and ITP and potential mediators in the European population.

Methods: Summary statistics of 10 common autoimmune diseases and ITP were extracted for analysis. Bidirectional two-sample MR and two-step MR were conducted.

Results: Multiple sclerosis (MS, inverse variance weighted [IVW]: odds ratio (OR)=5.840E+16, false discovery rate (FDR)=0.049), celiac disease (CeD, IVW: OR=1.173, FDR=0.023), systemic lupus erythematosus (SLE, IVW: OR=1.068, FDR=0.049), and autoimmune hyperthyroidism (AIH, IVW: OR=1.265, FDR=0.037) are risk factors for ITP. Rheumatoid arthritis (RA, IVW: OR=1.112, FDR=0.055) may be a potential risk factor. Crohn's disease (CD, IVW: OR=0.816, FDR=0.049), ulcerative colitis (UC, IVW: OR=0.709, FDR=0.042), and psoriasis (PsO, IVW: OR=1.690E - 04, FDR=0.042) are protective factors. No clear causal relationship between ankylosing spondylitis (AS, IVW: OR=1.016, FDR=0.553) and type 1 diabetes mellitus (T1DM, IVW: OR=1.035, FDR=0.577) and ITP. Immune cells act as mediators between CeD and ITP and CD and ITP.

Conclusion: This study clarified the relationship between some autoimmune diseases and ITP and the mediating role of immune cells.