Evaluating the association between immunological proteins and common intestinal diseases using a bidirectional two-sample Mendelian randomization study

Ziwei Wang; Qiuai Shu; Jian Wu; Yutong Cheng; Xiru Liang; Xindi Huang; Yixin Liu; Zhiwei Tao; Jinhai Wang; Feihu Bai; Na Liu; Ning Xie

doi:10.1016/j.cyto.2024.156788

Evaluating the association between immunological proteins and common intestinal diseases using a bidirectional two-sample Mendelian randomization study

Cytokine. 2024 Oct 27:184:156788. doi: 10.1016/j.cyto.2024.156788. Online ahead of print.

Authors

Ziwei Wang¹, Qiuai Shu², Jian Wu³, Yutong Cheng², Xiru Liang², Xindi Huang², Yixin Liu², Zhiwei Tao², Jinhai Wang², Feihu Bai⁴, Na Liu⁵, Ning Xie⁶

Affiliations

¹ Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Xi'an Jiaotong University, Xi'an, China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an, China; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
² Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Xi'an Jiaotong University, Xi'an, China.
³ State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
⁴ The Gastroenterology Clinical Medical Center of Hainan Province, Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China. Electronic address: [email protected].
⁵ Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Xi'an Jiaotong University, Xi'an, China. Electronic address: [email protected].
⁶ Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Xi'an Jiaotong University, Xi'an, China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an, China; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China. Electronic address: [email protected].

PMID: 39467484
DOI: 10.1016/j.cyto.2024.156788

Abstract

Dysregulation of intestinal homeostasis, characterized by imbalanced immunological proteins, contributes to the pathogenesis of common intestinal diseases, e.g., irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and colorectal cancer (CRC). However, the potential causal relationships between specific immunological proteins and these diseases remain to be fully elucidated. In this study, we employed the bidirectional two-sample Mendelian randomization analysis to infer potential causal relationships between representative immunological proteins and these intestinal diseases. Genome-wide association study (GWAS) summary statistics of IBS, IBD, and CRC were obtained from public databases and utilized in MR analysis. Multiple sensitivity analyses were performed to evaluate the robustness, with p-values adjusted using the Benjamini-Hochberg method for multiple comparisons. Our findings revealed a significant association between IL-1β (OR = 0.783, 95 % CI: 0.676 to 0.908, adjusted P = 0.048) and a decreased risk of IBS. Furthermore, genetic predisposition to IBS was related to the reduced levels of IL-25 (β = - 0.233, 95 % CI: -0.372 to -0.094, adjusted P = 0.047). Additionally, genetic predisposition to IBD was correlated with elevated levels of IL-6 (β = 0.046, 95 % CI: 0.022-0.069, adjusted P = 0.010). The levels of TNF-α (OR = 1.252, 95 % CI: 1.102 to 1.423, adjusted P = 0.047) were associated with an increased risk of CRC. Our study suggests associations between specific immunological proteins and intestinal diseases, which would provide valuable insights for developing targeted immunomodulation therapies for these conditions. Further investigation into underlying mechanisms remains a research priority in the future.

Keywords: Colorectal cancer; Immunological proteins; Inflammatory bowel disease; Intestinal homeostasis; Irritable bowel syndrome; Mendelian randomization.