Department of Gastrointestinal, Bariatric and Metabolic Surgery, West China-PUMC C.C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Immunol. 2023 Aug 18;14:1217444. doi: 10.3389/fimmu.2023.1217444. eCollection 2023.
The coronavirus disease 2019 (COVID-19) pandemic has exerted a profound influence on humans. Increasing evidence shows that immune response is crucial in influencing the risk of infection and disease severity. Observational studies suggest an association between COVID-19 and immunoglobulin G (IgG) N-glycosylation traits, but the causal relevance of these traits in COVID-19 susceptibility and severity remains controversial.
We conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between 77 IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity using summary-level data from genome-wide association studies (GWAS) and applying multiple methods including inverse-variance weighting (IVW), MR Egger, and weighted median. We also used Cochran's Q statistic and leave-one-out analysis to detect heterogeneity across each single nucleotide polymorphism (SNP). Additionally, we used the MR-Egger intercept test, MR-PRESSO global test, and PhenoScanner tool to detect and remove SNPs with horizontal pleiotropy and to ensure the reliability of our results.
We found significant causal associations between genetically predicted IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity. Specifically, we observed reduced risk of COVID-19 with the genetically predicted increased IgG N-glycan trait IGP45 (OR = 0.95, 95% CI = 0.92-0.98; FDR = 0.019). IGP22 and IGP30 were associated with a higher risk of COVID-19 hospitalization and severity. Two (IGP2 and IGP77) and five (IGP10, IGP14, IGP34, IGP36, and IGP50) IgG N-glycosylation traits were causally associated with a decreased risk of COVID-19 hospitalization and severity, respectively. Sensitivity analyses did not identify any horizontal pleiotropy.
Our study provides evidence that genetically elevated IgG N-glycosylation traits may have a causal effect on diverse COVID-19 outcomes. Our findings have potential implications for developing targeted interventions to improve COVID-19 outcomes by modulating IgG N-glycosylation levels.
2019 年冠状病毒病（COVID-19）大流行对人类产生了深远影响。越来越多的证据表明，免疫反应在影响感染风险和疾病严重程度方面至关重要。观察性研究表明，COVID-19 与免疫球蛋白 G（IgG）N-糖基化特征之间存在关联，但这些特征与 COVID-19 易感性和严重程度之间的因果关系仍存在争议。
我们进行了两样本 Mendelian 随机化（MR）分析，使用全基因组关联研究（GWAS）的汇总数据，应用包括逆方差加权（IVW）、MR Egger 和加权中位数在内的多种方法，探讨了 77 种 IgG N-糖基化特征与 COVID-19 易感性、住院和严重程度之间的因果关系。我们还使用 Cochran's Q 统计量和逐一剔除分析来检测每个单核苷酸多态性（SNP）的异质性。此外，我们使用 MR-Egger 截距检验、MR-PRESSO 全局检验和 PhenoScanner 工具来检测和去除具有水平多效性的 SNP，并确保结果的可靠性。
我们发现，遗传预测的 IgG N-糖基化特征与 COVID-19 易感性、住院和严重程度之间存在显著的因果关系。具体而言，我们观察到遗传预测的 IgG N-糖基化特征 IGP45 升高与 COVID-19 风险降低相关（OR=0.95，95%CI=0.92-0.98；FDR=0.019）。IGP22 和 IGP30 与 COVID-19 住院和严重程度的风险增加相关。两个（IGP2 和 IGP77）和五个（IGP10、IGP14、IGP34、IGP36 和 IGP50）IgG N-糖基化特征与 COVID-19 住院和严重程度的风险降低相关。敏感性分析未发现任何水平多效性。
本研究提供了遗传上升高的 IgG N-糖基化特征可能对多种 COVID-19 结局产生因果影响的证据。我们的发现为通过调节 IgG N-糖基化水平来改善 COVID-19 结局提供了靶向干预的潜在意义。
