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《工程(英文)》 >> 2023年 第26卷 第7期 doi: 10.1016/j.eng.2022.11.004

免疫球蛋白G N-糖基化与代谢特征之间的双向因果关联——一项孟德尔随机化研究

a Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China
b Centre for Precision Health, Edith Cowan University, Perth, WA 6027, Australia
c Centre for Biomedical Information Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
d School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China
e School of Medical and Health Sciences, Edith Cowan University, Perth, WA 6027, Australia

# These authors contributed equally to this work.

收稿日期: 2022-05-11 修回日期: 2022-10-07 录用日期: 2022-11-09 发布日期: 2022-12-07

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摘要

既往研究已发现免疫球蛋白G(immunoglobulin G, IgG)N-糖基化与代谢特征之间存在关联,但对于它们之间是否存在因果关联尚有待研究。本研究使用孟德尔随机化(Mendelian randomization, MR)研究方法,整合全基因组关联研究(genome-wide association studies, GWAS)和数量性状基因座(quantitative trait loci, QTL)数据,探究IgG N-糖基化与代谢特征之间的双向因果关联。在正向MR分析中,通过整合IgG N-糖基-QTL遗传变异与GWAS数据和代谢特征进行分析,分别发现59 个[包括影响体质指数(body mass index, BMI)的9 个IgG N-糖基(GP1 和GP7 等)和影响空腹血糖(fasting plasma glucose, FPG)的7 个IgG N-糖基(GP1 和GP5 等)等]和15 个[包括影响BMI的5 个IgG N-糖基(GP2 和GP11 等)和影响FPG的4 个
IgG N-糖基(GP1 和GP10 等)等]由遗传决定的IgG N-糖基在单样本和两样本MR研究中与代谢特征存在因果关联(全部P < 0.05)。相应地,对整合代谢特征-QTL-遗传变异与GWAS结果和IgG N-糖基进行MR分析的结果显示,在单样本和两样本MR研究中,分别发现72 个[包括影响GP1 的一个因果代谢特征,即高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)和5 个影响GP2 的因果代谢特征(FPG、收缩压(systolic blood pressure, SBP)等]和 4 个[包括影响GP3 的一个因果代谢特征(HDL-C)和影响GP9的一个代谢特征(HDL-C)等]由遗传决定的代谢特征与IgG N-糖基之间存在因果关联(全部P < 0.05)。值得注意的是,在单样本和两样本的MR分析中均发现了由遗传决定的高水平的GP11 与BMI水平增高存在因果关联[固定效应模型-Beta (SE):0.106 (0.051) 和 0.010 (0.005)],高水平的HDL-C与GP9 水平降低存在因果关联[−0.071 (0.022)和−0.306 (0.151)],且这一结果在单样本和两样本的meta 汇总分析中得到了进一步验证[固定效应模型-Beta(95%置信区间)分别为:0.0109 (0.0012, 0.0207) 和−0.0759 (−0.1186,
−0.0332)]。综上所述,本研究全面的双向MR分析提供了IgG N-糖基化与代谢特征之间双向因果关联的证据,在一定程度上揭示了IgG N-糖基化与代谢特征之间的生物学机制。

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