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确定干燥综合征与自身免疫性甲状腺疾病之间的遗传关联:一项双向两样本孟德尔随机化研究。

Identifying the Genetic Association Between Sjogren's Syndrome and Autoimmune Thyroid Disease: A Bidirectional Two-Sample Mendelian Randomization Study.

作者信息

Zhao Mingming, Zhang Yuanyuan, Sun Guoxun

机构信息

Department of Hematology and Rheumatology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.

出版信息

Int J Rheum Dis. 2024 Dec;27(12):e70008. doi: 10.1111/1756-185X.70008.

Abstract

BACKGROUND

Although observational studies have suggested a correlation between Sjogren's syndrome (SS) and autoimmune thyroid disease (AITD), a conclusive evidence supporting a causal relationship is still lacking. This study aims to explore the potential causal relationship between SS and AITD.

METHODS

Using genome-wide association studies, we performed a bidirectional two-sample Mendelian randomization (MR) analysis. In our analysis, the random-effects inverse variance weighted (IVW) method was predominantly employed, followed by several sensitivity analyses, which include heterogeneity, horizontal pleiotropy, outliers, and "leave-one-out" analyses.

RESULTS

In the study of the effect of SS on AITD, SS was associated with an increased risk of Hashimoto's thyroiditis (OR = 1.09, 95%CI 1.02-1.16, p = 0.01). The causal associations were supported by sensitivity analyses. In reverse MR analyses, Hashimoto's thyroiditis (OR = 1.24, 95% CI 1.08-1.42, p < 0.01) and Graves' disease (OR = 1.11, 95% CI 1.03-1.21, p < 0.01) were found to be risk factors for SS.

CONCLUSION

Our results support a bidirectional causal relationship between SS and Hashimoto's thyroiditis and a positive correlation of genetically predicted Graves' disease on the risk of SS.

摘要

背景

尽管观察性研究表明干燥综合征(SS)与自身免疫性甲状腺疾病(AITD)之间存在相关性,但仍缺乏支持因果关系的确凿证据。本研究旨在探讨SS与AITD之间潜在的因果关系。

方法

我们使用全基因组关联研究进行了双向两样本孟德尔随机化(MR)分析。在分析中,主要采用随机效应逆方差加权(IVW)方法,随后进行了多项敏感性分析,包括异质性、水平多效性、异常值和“留一法”分析。

结果

在SS对AITD影响的研究中,SS与桥本甲状腺炎风险增加相关(OR = 1.09,95%CI 1.02 - 1.16,p = 0.01)。敏感性分析支持了因果关联。在反向MR分析中,发现桥本甲状腺炎(OR = 1.24,95%CI 1.08 - 1.42,p < 0.01)和格雷夫斯病(OR = 1.11,95%CI 1.03 - 1.21,p < 0.01)是SS的危险因素。

结论

我们的结果支持SS与桥本甲状腺炎之间的双向因果关系,以及基因预测的格雷夫斯病与SS风险之间的正相关。

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