[Causal relationship between thyroid dysfunction and sepsis: a bidirectional two-sample Mendelian randomization].

Q3 Medicine
Jiawen Yuan, Dexiang Wang, Yuhao Hang, Qinyun Lu, Jian Wang, Jun Lu, Lu Cheng
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引用次数: 0

Abstract

Objective: To explore the causal relationship between thyroid dysfunction and sepsis based on the bidirectional two-sample Mendelian randomization (MR) method.

Methods: The genome-wide association study (GWAS) dataset were selected to screen single nucleotide polymorphisms (SNP) associated with thyroid dysfunction as instrumental variable (IV) for genetic variation, using hypothyroidism and hyperthyroidism as exposure factor and sepsis as outcome factor. Potential causal relationship between thyroid dysfunction and sepsis was analyzed using a bidirectional two-sample MR method primary analysis method of inverse-variance weighted (IVW). Potential pleiotropic analysis of SNP was performed using the MR Egger regression intercept test. Sensitivity analysis was performed using the "leave one out" test. Reverse MR method was used to prove the causal relationship.

Results: The GWAS data were screened based on the three main assumptions of MR, resulting in 101 SNP strongly associated with hypothyroidism and 10 SNP strongly associated with hyperthyroidism entering the MR analysis. The results of the MR using the IVW method showed that the risk of sepsis in individuals with hypothyroidism was 2.293 times higher than those without hypothyroidism [odds ratio (OR) = 2.293, 95% confidence interval (95%CI) was 1.199-4.382, P = 0.012]. There was no significant difference in the risk of sepsis between hyperthyroid and non-hyperthyroid populations (OR = 1.049, 95%CI was 0.999-1.100, P = 0.560). MR Egger regression intercept test showed that the included SNP did not have pleiotropy, and the MR-PRESSO test did not find outliers. Sensitivity analysis suggested that the results of MR were stable. The results of the reverse MR analysis showed that the reverse causal relationship between hyperthyroidism and sepsis was not proved (OR = 0.996, 95%CI was 0.988-1.004, P = 0.338), which further confirmed the robust MR analysis result.

Conclusions: The results of the bidirectional two-sample MR analysis show that hypothyroidism can increase the risk of sepsis onset, while there is no causal relationship between hyperthyroidism and sepsis.

[甲状腺功能障碍与败血症之间的因果关系:双向双样本孟德尔随机法]。
目的:探讨甲状腺功能障碍与败血症之间的因果关系:基于双向双样本孟德尔随机化(MR)方法,探讨甲状腺功能障碍与败血症之间的因果关系:选择全基因组关联研究(GWAS)数据集,以甲状腺功能减退症和甲状腺功能亢进症为暴露因素,以败血症为结局因素,筛选与甲状腺功能障碍相关的单核苷酸多态性(SNP)作为遗传变异的工具变量(IV)。采用反方差加权(IVW)的双向双样本 MR 法主要分析方法分析甲状腺功能障碍与败血症之间的潜在因果关系。使用 MR Egger 回归截距检验对 SNP 的潜在多向性进行了分析。使用 "漏掉一个 "检验进行敏感性分析。采用反向 MR 方法证明因果关系:根据 MR 的三个主要假设对 GWAS 数据进行筛选,结果有 101 个与甲状腺功能减退症密切相关的 SNP 和 10 个与甲状腺功能亢进症密切相关的 SNP 进入 MR 分析。采用IVW方法进行的MR结果显示,甲状腺功能减退症患者发生败血症的风险是非甲状腺功能减退症患者的2.293倍[比值比(OR)=2.293,95%置信区间(95%CI)为1.199-4.382,P=0.012]。甲状腺功能亢进人群与非甲状腺功能亢进人群发生败血症的风险无明显差异(OR = 1.049,95%CI 为 0.999-1.100,P = 0.560)。MR Egger回归截距检验表明,所包含的SNP不具有多向性,MR-PRESSO检验也未发现异常值。敏感性分析表明,MR 的结果是稳定的。反向 MR 分析结果显示,甲亢与败血症之间的反向因果关系未被证实(OR = 0.996,95%CI 为 0.988-1.004,P = 0.338),这进一步证实了 MR 分析结果的稳健性:双向双样本MR分析结果表明,甲状腺功能减退可增加脓毒症发病风险,而甲状腺功能亢进与脓毒症之间没有因果关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Zhonghua wei zhong bing ji jiu yi xue
Zhonghua wei zhong bing ji jiu yi xue Medicine-Critical Care and Intensive Care Medicine
CiteScore
1.00
自引率
0.00%
发文量
42
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