背景:免疫球蛋白G(IgG)N-糖基化被认为是衰老和各种病理状况的潜在生物标志物。然而,IgGN-糖基化的这些变化是衰老过程的结果还是原因尚不清楚.本研究旨在使用孟德尔随机化(MR)分析研究IgGN-糖基化与衰老之间的因果关系。
方法:我们利用了与IgGN-糖基化性状相关的遗传变异,脆弱指数(FI),和白细胞端粒长度(LTL)来自先前对欧洲血统个体的全基因组关联研究(GWAS)。进行了双样本和多变量MR分析,采用逆方差加权(IVW)方法。进行敏感性分析以评估潜在的混杂因素。
结果:使用IVW方法,我们在两样本MR分析中发现GP14与FI(β0.026,95%CI0.003~0.050,p=0.027)和LTL(β-0.020,95%CI-0.037~-0.002,p=0.029)之间存在因果关系的暗示性证据.在多变量MR分析中,发现GP23和FI(β-0.119,95%CI-0.219至-0.019,p=0.019)以及GP2和LTL(β0.140,95%CI0.020至0.260,p=0.023)的提示证据。
结论:结论:我们的结果支持GP23水平降低对晚期衰老状态的潜在因果效应.需要额外的验证以进一步证实糖基化与衰老之间的因果关系。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.