甲状腺毒症与腰痛风险：一项孟德尔随机化研究的启示

Thyrotoxicosis and Risk of Low Back Pain: Insights from a Mendelian Randomization Study

摘要: 背景：观察性研究发现甲状腺毒症与腰痛之间存在关联，但二者的因果关系尚不明确。目的：本研究旨在利用孟德尔随机化方法探讨甲状腺毒症与腰痛之间的遗传因果关系。方法：本研究所有数据均基于全基因组关联研究的汇总数据。通过逆方差加权法获得的结果作为主要结局指标，同时辅以MR-Egger、加权中位数、加权模型和简单模型作为补充结局，探究甲状腺毒症与腰痛之间潜在的因果关系。此外，还进行了一系列敏感性分析(包括Cochran’s Q检验、MR-Egger截距检验、MR-PRESSO方法及留一法分析)以排除有影响的工具变量，进一步评估孟德尔随机化分析的准确性。结果：逆方差加权分析结果表明，甲状腺毒症(OR = 1.048, 95% CI: 1.005~1.093, P = 0.030)与腰痛存在正向关联。在孟德尔随机化分析使用的单核苷酸多态性中未观察到明显的水平多效性或异质性。结论：本研究证实患有甲状腺毒症的个体在遗传上易患腰痛。这些发现表明对甲状腺毒症患者进行早期腰痛筛查或有助于降低患病风险。

Abstract: Background: Observational studies have found a connection between thyrotoxicosis and low back pain. However, the causal relationship between them remains unclear. Objectives: This study aims to explore the genetic causal relationship between thyrotoxicosis and low back pain using Mendelian randomization. Methods: All data in this study are based on summary data from genome-wide association studies. Results obtained through the inverse variance weighted method are used as the primary outcome measure, while MR-Egger, weighted median, weighted model, and simple model serve as supplementary outcomes to explore the potential causal relationship between thyrotoxicosis and low back pain. Additionally, a series of sensitivity analyses were conducted, including Cochran’s Q test, the MR-Egger intercept test, the MR-PRESSO method, and leave-one-out analysis to exclude influential instrumental variables, aiming to further assess the accuracy of the Mendelian randomization analysis. Results: The results of the inverse variance weighted analysis indicated a positive association between thyrotoxicosis (OR = 1.048, 95% CI: 1.005~1.093, P = 0.030) and low back pain. No significant horizontal pleiotropy or heterogeneity was observed among the Single Nucleotide Polymorphisms used in the Mendelian randomization analysis. Conclusion: This study demonstrates that individuals with thyrotoxicosis are genetically predisposed to low back pain. These findings suggest that early screening for low back pain in patients with thyrotoxicosis may help reduce the risk of developing this condition.