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  • IDDF2024-ABS-0401 Causal relationship between plasma N-glycans and inflammatory bowel diseases: a bi-directional two-sample mendelian randomization study

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Clinical Gastroenterology
IDDF2024-ABS-0401 Causal relationship between plasma N-glycans and inflammatory bowel diseases: a bi-directional two-sample mendelian randomization study
  1. Hao Wang1,
  2. Xueping Huang2,
  3. Xingang Li3,
  4. Haiyun Shi2
  1. 1Department of Clinical Epidemiology and Evidence-Based Medicine, Beijing Clinical Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, China
  2. 2Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China
  3. 3Center for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia

Abstract

Background Glycans play a significant role in inflammation diseases, and observational studies described associations between plasma N-glycans and inflammatory bowel diseases (IBD), but the exact causal relationships between them remain unclear. Therefore, a bidirectional two-sample Mendelian Randomization (MR) study was conducted to explore the potential causality.

Methods Summary statistics for N-glycans were obtained from a genome-wide association study (GWAS) meta-analysis with 3811 subjects of European ancestry, and summary data for IBD was obtained from 30,713 IBD cases and 338,106 controls of European ancestry. Bi-directional univariable MR analyses were conducted to infer the causal association between them. The inverse-variance-weighted (IVW) analysis was performed as the primary analysis, followed by several sensitivity analyses to explore the stability of the results. (IDDF2024-ABS-0401 Figure 1. Study design and instrumental variables (IVs) selection flow)

Results As shown in Figure 2 (IDDF2024-ABS-0401 Figure 2. Forest plot for the causal effect of plasma N-glycans on IBD and vice versa), three putatively causal N-glycans for IBD were identified in the IVW method. The levels of plasma glycan peak 18 (PGP18) (odds ratio (OR) = 0.961, 95% confidence interval (CI): 0.926 - 0.997, P-value = 0.039), PGP23 (OR = 0.963, 95% CI: 0.933 - 0.993, P-value = 0.015) and PGP25 (OR = 0.960, 95% CI: 0.932 - 0.988, P-value = 0.005) decreased the risk of IBD. Reverse MR showed that IBD was causally associated with PGP15 (OR = 0.917, 95% CI: 0.866 - 0.970, P-value = 0.001), PGP24 (OR = 1.061, 95% CI: 1.002 – 1.123, P-value = 0.029) and PGP30 (OR = 1.063, 95% CI: 1.002 – 1.127, P-value = 0.024). The MR pleiotropy residual sum and outlier (MR-PRESSO) global test and the intercept of MR-Egger regression indicated no evidence of horizontal pleiotropy.

Abstract IDDF2024-ABS-0401 Figure 1
Abstract IDDF2024-ABS-0401 Figure 1

Study design and instrumental variables (IVs) selection flow.

Abstract IDDF2024-ABS-0401 Figure 2
Abstract IDDF2024-ABS-0401 Figure 2

Forest plot for the causal effect of plasma N-glycans on IBD and vice versa.

Conclusions N-glycans in plasma would be causally associated with IBD and vice versa. The findings prompt further investigation into the functional role of N-glycans in the pathogenesis of IBD, offering potential insights for the development of new serological biomarkers and intervention targets to further improve the diagnosis and treatment of IBD.

https://doi.org/10.1136/gutjnl-2024-IDDF.330

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