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Although the association between immunoglobulin G (IgG) N-glycosylation and metabolic traits has been previously identified, the causal association between them remains unclear. In this work, we used Mendelian randomization (MR) analysis to integrate genome-wide association studies (GWASs) and quantitative trait loci (QTLs) data in order to investigate the bidirectional causal association of IgG N-glycosylation with metabolic traits. In the forward MR analysis, 59 (including nine putatively causal glycan peaks (GPs) for body mass index (BMI) (GP1, GP6, etc.) and seven for fasting plasma glucose (FPG) (GP1, GP5, etc.)) and 15 (including five putatively causal GPs for BMI (GP2, GP11, etc.) and four for FPG (GP1, GP10, etc.)) genetically determined IgG N-glycans were identified as being associated with metabolic traits in one- and two-sample MR studies, respectively, by integrating IgG N-glycan-QTL variants with GWAS results for metabolic traits (all P

Observational studies support that altered immunoglobulin G (IgG) N-glycosylation and inflammatory factors are associated with cardiometabolic diseases (CMDs); nevertheless, the causality between them remains unclear. Two-sample Mendelian randomization (MR) analyses were conducted to systematically investigate the bidirectional causality between IgG N-glycans and nine CMDs in both East Asians and Europeans. In the forward MR analysis, the univariable MR analysis presented suggestive causality of 14 and eight genetically instrumented IgG N-glycans with CMDs in East Asians and Europeans, respectively; the multivariable MR analysis showed that ten and 11 pairs of glycan-CMD associations were identified in East Asian and European populations, respectively. In the reverse MR analysis, based on East Asians and Europeans, the univariable MR analysis presented suggestive causality of seven and 12 genetically instrumented CMDs with IgG N-glycans, respectively; the multivariable MR analysis presented that six and five CMD-glycan causality were found in East Asian and Europeans, respectively. The comprehensive MR analyses provide suggestive evidence of bidirectional causality between IgG N-glycans and CMDs. This work helps to understand the molecular mechanism of the occurrence/progression of CMDs, optimize existing and develop new strategies to prevent CMDs, and contribute to the early identification of high-risk groups of CMDs. • The MR analysis showed suggestive bidirectional causality of IgG N-glycans with CMDs. • This bidirectional causality of IgG N-glycans with CMDs may be mediated by inflammatory factors. • The study provides new insights into the mechanism between IgG N-glycans and CMDs. [ABSTRACT FROM AUTHOR]