IDDF2024-ABS-0393 Causal relationship between peripheral immune cell counts and inflammatory bowel diseases: a bidirectional two-sample mendelian randomization study

<h3>Background</h3> 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 bidirectional two-sample Mendelian Randomization (MR) study is conducted to explore this potential causality. <h3>Methods</h3> GWAS summary data for peripheral immune cell counts were obtained from the 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 (IDDF2024-ABS-0393 Figure 1. The flowchart providing an overview of instrumental variables (IVs) selection process and MR analysis plan). <h3>Results</h3> 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 IBD patients, with specific increase 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) (IDDF2024-ABS-0393 Figure 2. Forest plot for the causal effect of peripheral immune cell counts on IBD and vice versa). <h3>Conclusions</h3> These findings imply that increased 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.