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Immunoglobulin G (IgG) N-glycosylation is considered a potential biomarker for aging and various pathological conditions. However, whether these changes in IgG N-glycosylation are a consequence or a contributor to the aging process remains unclear. This study aims to investigate the causality between IgG N-glycosylation and aging using Mendelian randomization (MR) analysis. We utilized genetic variants associated with IgG N-glycosylation traits, the frailty index (FI), and leukocyte telomere length (LTL) from a previous genome-wide association study (GWAS) on individuals of European ancestry. Two-sample and multivariable MR analyses were conducted, employing the inverse-variance weighted (IVW) method. Sensitivity analyses were performed to assess potential confounding factors. Using the IVW method, we found suggestive evidence of a causal association between GP14 and FI (β 0.026, 95% CI 0.003 to 0.050, p = 0.027) and LTL (β -0.020, 95% CI -0.037 to -0.002, p = 0.029) in the two-sample MR analysis. In the multivariable MR analysis, suggestive evidence was found for GP23 and FI (β -0.119, 95% CI -0.219 to -0.019, p = 0.019) and GP2 and LTL (β 0.140, 95% CI 0.020 to 0.260, p = 0.023). In conclusion, our results supported a potentially causal effect of lower GP23 levels on an advanced aging state. Additional verification is required to further substantiate the causal relationship between glycosylation and aging.

Citation

Wenxin Sun, Xuening Jian, Jie Zhang, Xiaoni Meng, Haotian Wang, Deqiang Zheng, Lijuan Wu, Youxin Wang. The Causality between Human Immunoglobulin G (IgG) N-Glycosylation and Aging: A Mendelian Randomization Study. Molecules (Basel, Switzerland). 2024 Mar 14;29(6)

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PMID: 38542917

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