Abstract

Background: Evidence suggests that immunoglobulin G (IgG) N-glycosylation is associated with ischemic stroke (IS). However, the causality of IgG N-glycosylation for IS remains unknown. Methods: Two-sample Mendelian randomization (MR) analyses were performed to investigate the potential causal effects of genetically determined IgG N-glycans on IS using publicly available summarized genetic data from East Asian and European populations. Genetic instruments were used as proxies for IgG N-glycan traits. IgG N-glycans were analysed using ultra-performance liquid chromatography. Four complementary MR methods were performed, including the inverse variance weighted method (IVW), MR‒Egger, weighted median and penalized weighted median. Furthermore, to further test the robustness of the results, MR based on Bayesian model averaging (MR-BMA) was then applied to select and prioritize IgG N-glycan traits as risk factors for IS. Results: After correcting for multiple testing, in two-sample MR analyses, genetically predicted IgG N-glycans were unrelated to IS in both East Asian and European populations, and the results remained consistent and robust in the sensitivity analysis. Moreover, MR-BMA also showed consistent results in both East Asian and European populations. Conclusions: Contrary to observational studies, the study did not provide enough genetic evidence to support the causal associations of genetically predicted IgG N-glycan traits and IS, suggesting that N-glycosylation of IgG might not directly involve in the pathogenesis of IS.

中文翻译：

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揭示免疫球蛋白 G N-聚糖在缺血性中风中的遗传因果关系

摘要

背景：有证据表明免疫球蛋白 G (IgG) N-糖基化与缺血性中风 (IS) 相关。然而，IgG N-糖基化与 IS 的因果关系仍不清楚。方法：使用来自东亚和欧洲人群的公开汇总遗传数据进行两样本孟德尔随机化 (MR) 分析，以研究遗传确定的 IgG N-聚糖对 IS 的潜在因果影响。遗传仪器被用作 IgG N-聚糖特征的代表。使用超高效液相色谱分析 IgG N-聚糖。进行了四种互补的 MR 方法，包括反方差加权法 (IVW)、MR-Egger、加权中位数和惩罚加权中位数。此外，为了进一步测试结果的稳健性，然后应用基于贝叶斯模型平均 (MR-BMA) 的 MR 来选择和优先考虑 IgG N-聚糖特征作为 IS 的危险因素。结果：在对多个测试进行校正后，在两个样本的 MR 分析中，在东亚和欧洲人群中，基因预测的 IgG N-聚糖与 IS 无关，并且结果在敏感性分析中保持一致和稳健。此外，MR-BMA 在东亚和欧洲人群中也显示出一致的结果。结论：与观察性研究相反，该研究没有提供足够的遗传学证据来支持基因预测的 IgG N-聚糖特征与 IS 之间的因果关系，表明 IgG 的 N-糖基化可能不直接参与 IS 的发病机制。