Causal Relationship between Peripheral Immune Cell Counts and Inflammatory Bowel Diseases: A Bi-directional Two-sample Mendelian Randomization Study

Background Observational studies have described an association between peripheral immune cell counts and inflammatory bowel diseases (IBD), but the exact causal relationship between them remains unclear. Therefore, a bi-directional two-sample Mendelian Randomization (MR) study was conducted to explore this potential causality. Methods GWAS summary data for peripheral immune cell counts were obtained from Blood Cell Consortium with 563,085 subjects of European ancestry, and data for IBD, Cronh’s disease (CD), and ulcerative colitis (UC) were obtained from five independent cohorts with 368,819 subjects of European ancestry. Single-variable Mendelian randomization (SVMR) was performed and followed by multivariable Mendelian randomization (MVMR) to assess the causal effects of peripheral immune cell counts on IBD risk. Results SVMR estimates showed that genetically predicted higher leukocytes [odds ratio (OR): 1.225, 95% confidence interval (CI): 1.027–1.452, P  = 0.027] and neutrophils (OR: 1.281, 95% CI: 1.044–1.572, P  = 0.018) increased risk of CD, and higher eosinophils increased risk of UC (OR: 1.288, 95% CI: 1.067–1.412, P  = 0.005). In MVMR, the effects of neutrophils (OR: 1.653, 95% CI: 1.139–2.405, P  = 0.010) and eosinophils (OR: 1.303, 95% CI: 1.016–1.668, P  = 0.040) were still significant. Reverse MR analysis showed higher basophils (OR: 1.013, 95% CI: 1.001–1.014, P  = 0.049) and eosinophils (OR: 1.012, 95% CI: 1.004–1.023, P  = 0.027), and lower lymphocytes (OR: 0.993, 95% CI: 0.984-0,997, P  = 0.015) in patients with IBD, with specific increases in neutrophils for CD (OR: 1.011, 95% CI: 1.005–1.014, P  = 0.044) and basophils for UC (OR: 1.012, 95% CI: 1.004–1.023, P  = 0.013). Conclusions These findings imply that increased peripheral neutrophil and eosinophil counts are potential causal risk factors for IBD, and IBD could affect the level of basophil, neutrophil, and lymphocyte count in turn. Our results may offer potential insights for the development of biomarkers and targeted treatment strategies for IBD.