Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, 10 Xitoutiao, Beijing, 100069, China.
Centre for Biomedical Information Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.
Mol Med. 2022 Sep 14;28(1):114. doi: 10.1186/s10020-022-00543-z.
Immunoglobulin G (IgG) N-glycans have been shown to be associated with the risk of type 2 diabetes (T2D) and its risk factors. However, whether these associations reflect causal effects remain unclear. Furthermore, the associations of IgG N-glycans and inflammation are not fully understood.
We examined the causal associations of IgG N-glycans with inflammation (C-reactive protein (CRP) and fibrinogen) and T2D using two-sample Mendelian randomization (MR) analysis in East Asian and European populations. Genetic variants from IgG N-glycan quantitative trait loci (QTL) data were used as instrumental variables. Two-sample MR was conducted for IgG N-glycans with inflammation (75,391 and 18,348 participants of CRP and fibrinogen in the East Asian population, 204,402 participants of CRP in the European population) and T2D risk (77,418 cases and 356,122 controls of East Asian ancestry, 81,412 cases and 370,832 controls of European ancestry).
After correcting for multiple testing, in the East Asian population, genetically determined IgG N-glycans were associated with a higher risk of T2D, the odds ratios (ORs) were 1.009 for T2D per 1- standard deviation (SD) higher GP5, 95% CI = 1.003-1.015; P = 0.0019; and 1.013 for T2D per 1-SD higher GP13, 95% CI = 1.006-1.021; P = 0.0005. In the European population, genetically determined decreased GP9 was associated with T2D (OR = 0.899 per 1-SD lower GP9, 95% CI: 0.845-0.957). In addition, there was suggestive evidence that genetically determined IgG N-glycans were associated with CRP in both East Asian and European populations after correcting for multiple testing, but no associations were found between IgG N-glycans and fibrinogen. There was limited evidence of heterogeneity and pleiotropy bias.
Our results provided novel genetic evidence that IgG N-glycans are causally associated with T2D.
免疫球蛋白 G（IgG）N-聚糖已被证明与 2 型糖尿病（T2D）及其危险因素有关。然而，这些关联是否反映了因果关系尚不清楚。此外，IgG N-聚糖与炎症的关联尚不完全清楚。
我们使用东亚和欧洲人群的两样本 Mendelian 随机化（MR）分析，研究了 IgG N-聚糖与炎症（C 反应蛋白（CRP）和纤维蛋白原）和 T2D 的因果关联。使用 IgG N-聚糖定量性状基因座（QTL）数据中的遗传变异作为工具变量。对东亚人群中 IgG N-聚糖与炎症（CRP 为 75391 人，纤维蛋白原为 18348 人；欧洲人群中 CRP 为 204402 人）和 T2D 风险（东亚血统 77418 例，356122 例对照；欧洲血统 81412 例，370832 例对照）进行了两样本 MR。
在东亚人群中，经过多重检验校正后，遗传决定的 IgG N-聚糖与 T2D 风险增加相关，每增加 1-SD IgG N-聚糖，T2D 的优势比（OR）为 1.009（95%CI=1.003-1.015；P=0.0019），每增加 1-SD IgG N-聚糖，T2D 的 OR 为 1.013（95%CI=1.006-1.021；P=0.0005）。在欧洲人群中，遗传决定的 GP9 降低与 T2D 相关（每降低 1-SD GP9，T2D 的 OR 为 0.899（95%CI：0.845-0.957））。此外，在经过多重检验校正后，有迹象表明遗传决定的 IgG N-聚糖与东亚和欧洲人群中的 CRP 相关，但 IgG N-聚糖与纤维蛋白原之间没有关联。存在异质性和多效性偏见的有限证据。
我们的研究结果提供了新的遗传证据，表明 IgG N-聚糖与 T2D 有因果关系。
