Document Type

Journal Article

Publication Title

Diabetology and Metabolic Syndrome








Centre for Precision Medicine




National Natural Science Foundation of China


Wang, H., Li, Y., Cao, W., Zhang, J., Cao, M., Meng, X., ... & Wang, Y. (2023). Leveraging IgG N-glycosylation to infer the causality between T2D and hypertension. Diabetology & Metabolic Syndrome, 15, 80.


Background: Observational studies demonstrated a bidirectional association between type 2 diabetes (T2D) and hypertension, whereas Mendelian randomization (MR) analyses supported the causality from T2D to hypertension but not causal from hypertension to T2D. We previously found that IgG N-glycosylation is associated with both T2D and hypertension, and thus IgG N-glycosylation might link the causality between them. Methods: We carried out a genome-wide association study (GWAS) to identify IgG N-glycosylation-quantitative-trait loci (QTLs) integrating GWAS for T2D and hypertension and then performed bidirectional univariable and multivariable MR analyses to infer the causal association among them. The inverse-variance-weighted (IVW) analysis was performed as the primary analysis, followed by some sensitivity analyses to explore the stability of the results. Results: Six putatively causal IgG N-glycans for T2D and four for hypertension were identified in the IVW method. Genetically predicted T2D increased the risk of hypertension (odds ratio [OR] = 1.177, 95% confidence interval (95% CI) = 1.037–1.338, P = 0.012) and vice versa (OR = 1.391, 95% CI = 1.081–1.790, P = 0.010). Multivariable MR showed that T2D remained at risk effect with hypertension ([OR] = 1.229, 95% CI = 1.140–1.325, P = 7.817 × 10–8) after conditioning on T2D-related IgG-glycans. Conversely, hypertension was associated with higher T2D risk (OR = 1.287, 95% CI = 1.107–1.497, P = 0.001) after adjusting for related IgG-glycans. No evidence of horizontal pleiotropy was observed, as MR‒Egger regression provided P values for intercept > 0.05. Conclusion: Our study validated the mutual causality between T2D and hypertension from the perspective of IgG N-glycosylation, further validating the “common soil” hypothesis underlying the pathogenesis of T2D and hypertension.



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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.