甲状腺功能障碍与静脉血栓之间的关系:1项双样本双向孟德尔随机化研究

Association between thyroid dysfunction and venous thrombosis： a two-sample bidirectional Mendelian randomization study

摘要

目的 探究甲状腺功能障碍与静脉血栓栓塞症之间的因果关系，为甲状腺功能障碍与静脉血栓栓塞症发病风险提供遗传学证据支持。 方法 采用全基因组关联研究（genome-wide association studies，GWAS）数据进行分析。本研究选择促甲状腺素（thyroid stimulating hormone，TSH）、游离甲状腺素（free thyroxine，FT4）、甲状腺功能亢进（hyperthyroidism）和甲状腺功能减退（hypothyroidism）作为暴露因素。结局变量为静脉血栓栓塞症（venous thromboembolism，VTE），包括深静脉血栓（deep vein thrombosis，DVT）和肺栓塞（pulmonary embolism，PE）。逆方差加权法（inverse-variance weighted，IVW）是评估暴露与结局之间因果关系的主要方法，并辅以MR-Egger、加权中位数法（Weighted median）、简易法（Simple mode）进行分析，同时Cochrane’s Q检验作为敏感性分析方法。 结果 IVW显示甲亢与VTE（OR=1.074，95%CI=1.016~1.135，P=0.011）、PE（OR=1.054，95%CI=1.012~1.098，P=0.011）和DVT（OR=1.068，95%CI=1.014~1.126，P=0.013）存在正向的因果关系。 结论 研究基于遗传数据认为甲状腺功能障碍与静脉血栓栓塞症存在因果关系，甲状腺功能亢进会增加静脉血栓发生的风险。

Abstract

Objective To investigate the causal relationship between thyroid dysfunction and venous thrombosis，and to provide genetic evidence for the association between thyroid dysfunction and the risk of venous thrombosis. Methods The data of genome-wide association studies were used for analysis. In this study，thyroid stimulating hormone，free thyroxine，hyperthyroidism，and hypothyroidism were selected as exposure factors，and venous thromboembolism（VTE） was selected as the outcome variable，including deep vein thrombosis（DVT） and pulmonary embolism（PE）. The inverse-variance weighted（IVW） method was used for assessing the causal relationship between exposure factors and outcome variables，assisted by the MR-Egger，weighted median，and simple mode methods，and the Cochrane’s Q test was used for sensitivity analysis. Results The IVW analysis showed that hyperthyroidism had a positive causal relationship with VTE（odds ratio ［OR］=1.074，95%CI=1.016～1.135，P=0.011），PE（OR=1.054，95%CI=1.012～1.098，P=0.011），and DVT（OR=1.068，95%CI=1.014～1.126，P=0.013）. Conclusion Based on genetic data，this study shows that there is a causal relationship between thyroid dysfunction and VTE，and hyperthyroidism may increase the risk of VTE.

关键词

甲状腺功能障碍 / 静脉血栓栓塞症 / 孟德尔随机化 / 全基因组关联研究

Key words

thyroid dysfunction / venous thromboembolism / Mendelian Randomization / genome-wide association studies