Mendelian randomization study of circulating leukocytes counts reveals causal associations with inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic recurrent IBD, whose cause involves the interaction between genetic and environmental factors. Although there is a recognized link between immune response and IBD, the causal relationship between circulating immune cell counts and IBD remains controversial. This study aimed to elucidate the causal relationship between genetically predicted circulating immune cell counts and IBD. We conducted a bidirectional 2-sample Mendelian randomization (MR) study using aggregated statistics from genome-wide association studies. The causal relationship between 5 circulating leukocytes cells (monocytes, lymphocytes, eosinophils, basophils and neutrophils) counts and IBD, including ulcerative colitis (UC) and Crohn disease (CD) was analyzed. Horizontal pleiotropy test and heterogeneity test were used to ensure the stability of the results. Our findings indicated that monocytes, lymphocytes, eosinophils, and basophils count were not significantly associated with IBD, however, elevated circulating neutrophils count was significantly associated with higher risk of IBD [odds ratio (OR) = 1.0017; 95% confidence interval (CI) = 1.0004-1.003; P = .009] and UC [OR = 2.465; 95% CI = 1.236-4.916; P = .01]. In addition, we also found that IBD [OR: 12.07; 95% CI = 1.909-76.316; P = .008] and CD [OR = 1.014; 95% CI = 1.004-1.023; P = .005] were significantly associated with higher circulating neutrophils count in reverse MR. This MR study provides genetic evidence for the causal relationship between the genetically predicted increase in circulating neutrophils count and the risk of IBD (UC and CD). This finding stresses the need for further exploring physiological functions of neutrophils in order to develop effective strategies against IBD.