Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China.
Department of Health Management, the Second Affiliated Hospital, the Fourth Military Medical University, Xi'an, China.
Glycoconj J. 2023 Aug;40(4):413-420. doi: 10.1007/s10719-023-10127-6. Epub 2023 Jun 21.
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.
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.
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.
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.
有证据表明，免疫球蛋白 G（IgG）N-糖基化与缺血性脑卒中（IS）有关。然而，IgG N-糖基化与 IS 之间的因果关系尚不清楚。
采用两样本 Mendelian 随机化（MR）分析，利用东亚和欧洲人群中公开的汇总遗传数据，探讨遗传决定的 IgG N-聚糖对 IS 的潜在因果作用。遗传工具被用作 IgG N-聚糖特征的替代物。使用超高效液相色谱法分析 IgG N-聚糖。进行了四种互补的 MR 方法，包括逆方差加权法（IVW）、MR-Egger、加权中位数和惩罚加权中位数。此外，为了进一步检验结果的稳健性，然后应用基于贝叶斯模型平均的 MR（MR-BMA）来选择和优先考虑 IgG N-聚糖特征作为 IS 的风险因素。
在两样本 MR 分析中，经过多重检验校正后，遗传预测的 IgG N-聚糖与东亚和欧洲人群中的 IS 均无关，敏感性分析结果也一致且稳健。此外，MR-BMA 在东亚和欧洲人群中也得到了一致的结果。
与观察性研究相反，该研究没有提供足够的遗传证据支持遗传预测的 IgG N-聚糖特征与 IS 之间的因果关系，这表明 IgG 的 N-糖基化可能不会直接参与 IS 的发病机制。
