南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (8): 1396-1401.doi: 10.12122/j.issn.1673-4254.2023.08.17

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1型糖尿病可能增加甲状腺毒症的风险：基于两样本孟德尔随机化方法

占雯婕，赵 玲   

  1. 广州中医药大学第二临床医学院，广东 广州 510006；广州中医药大学第二附属医院，广东 广州 510006
  • 出版日期:2023-08-20 发布日期:2023-09-13

Type 1 diabetes mellitus is likely to increase the risk of thyrotoxicdsis: a two-sample Mendelian randomization study

ZHAN Wenjie, ZHAO Ling   

  1. Second Clinical College of Guangzhou, University of Chinese Medicine, Guangzhou 510006, China; The Second Affiliated Hospital of Guangzhou, University of Chinese Medicine, Guangzhou 510006, China
  • Online:2023-08-20 Published:2023-09-13

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摘要： 目的 采用两样本孟德尔随机化（MR）方法探究 1 型糖尿病（T1DM）和甲状腺毒症之间的关系。方法 利用IEUOpenGWAS project网站获取T1DM及甲状腺毒症的全基因组关联研究（GWAS）数据。筛选与T1DM密切相关且独立的单核苷酸多态性（SNPs）作为工具变量（IVs），用MR-PRESSO进行离群值检验并剔除离群值，分别运用逆方差加权法（IVW）、MR-Egger回归、加权众数法（WM）和加权中位数法（WME）进MR分析，以OR值及95% CI评价T1DM与甲状腺毒症之间是否存在关联。分别采用IVW和MR-Egger法进行Cochran Q 和Rücker Q异质性检验，用Egger-intercept法进行多效性检验、逐个剔除检验进行敏感性分析，并计算F值以评估是否存在弱IVs偏倚。结果 4种MR方法所得结果显示，整体人群中T1DM与甲状腺毒症具有正向的因果关系，且具有显著的统计学意义，IVW、MR-Egger回归、加权模型和WME计算所得OR值和95% CI分别为1.077（95% CI 1.046~1.109）、1.076（95% CI 1.031~1.124）、1.082（95% CI 1.048~1.118）、1.090（95% CI 1.052~1.129）。异质性检验结果分别为P=0.127和P=0.155，即不存在异质性；Egger-intercept结果为P=0.965，即不存在多效性；敏感性分析显示结果稳定；全部F值大于10，提示不存在弱IVs偏倚。结论 T1DM可能会增加甲状腺毒症的风险。

关键词: 1型糖尿病；甲状腺毒症；孟德尔随机化

Abstract: Objective To explore the relationship between type 1 diabetes (T1DM) and thyrotoxicosis using two-sample Mendelian randomization (MR) method. Methods Based on the data from a large-scale metabolome-based genome-wide association study (GWAS), we investigated the causality between T1DM and thyrotoxicosis using inverse variance-weighted (IVW) method, MR-Egger regression, weighted Mode (WM) method and weighted median (WME) method. Single nucleotide polymorphisms (SNPs) closely related to T1DM were screened as the instrumental variables (IVs). Outlier testing was performed using MR-PRESSON to reject the outliers. Heterogeneity tests, horizontal pleiotropy and sensitivity tests were performed to evaluate the reliability and stability of the results, and F-values were calculated to assess the presence of weak IVs bias. Results There was a positive causal effect between T1DM and thyrotoxicosis in the total samples analyzed with the 4 MR methods. The ORs and 95% CIs calculated by IVW, MR-Egger regression, WM and WME methods were 1.077 (95% CI: 1.046?1.109), 1.076 (95% CI: 1.031?1.124), 1.082 (95% CI: 1.048?1.118), and 1.090 (95% CI: 1.052?1.129), respectively. The results of the heterogeneity test were P=0.127 and P=0.155, respectively, suggesting the absence of heterogeneity. Egger-intercept result was P=0.965, indicating the absence of pleiotropy. Leave-one-out analysis showed stable results. All the F values were greater than 10, indicating that there was no weak IVs bias. Conclusion T1DM is likely to increase the risk of thyrotoxicosis.

Key words: type 1 diabetes; thyrotoxicosis; Mendelian randomization