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

<h3>Background</h3> 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. <h3>Methods</h3> 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) <h3>Results</h3> 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, <i>P</i>-value = 0.039), PGP23 (OR = 0.963, 95% CI: 0.933 - 0.993, <i>P</i>-value = 0.015) and PGP25 (OR = 0.960, 95% CI: 0.932 - 0.988, <i>P</i>-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, <i>P</i>-value = 0.001), PGP24 (OR = 1.061, 95% CI: 1.002 – 1.123, <i>P</i>-value = 0.029) and PGP30 (OR = 1.063, 95% CI: 1.002 – 1.127, <i>P</i>-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. <h3>Conclusions</h3> 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.