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端粒长度及其与亚洲人群系统性红斑狼疮的关联:一项孟德尔随机研究。

Telomere length and its association with systemic lupus erythematosus in an Asian population: A Mendelian randomization study.

机构信息

Department of Epidemiology, School of Public Health (Shenzhen), Sun Yat-Sen University, Shenzhen, China.

Department of Epidemiology, School of Public Health, Kunming Medical University, Kunming, China.

出版信息

Lupus. 2023 Sep;32(10):1222-1226. doi: 10.1177/09612033231195953. Epub 2023 Aug 19.

Abstract

OBJECTIVES

To investigate whether shorter telomere length is a causal risk factor for systemic lupus erythematosus (SLE) in the Asian population.

METHODS

We applied the two-sample Mendelian randomization (MR) method to the pooled statistics from a genome-wide association study (GWAS) of 6,707 SLE cases and 16,047 controls. We selected nine single-nucleotide polymorphisms (SNPs) with genome-wide significance as instrumental variables for telomere length. The main analysis was carried out by the random-effects inverse-variance weighted (IVW) method. Horizontal pleiotropy was evaluated by the intercept of MR-Egger regression.

RESULTS

A potentially causal relationship between longer genetically predicted telomere length and increased risk of systemic lupus erythematosus (OR = 1.72, 95%CI: 1.21, 2.46, = 0.01) was observed. The MR-Egger regression demonstrated an intercept proximal to zero (intercept = 0.017, = 0.69), which does not provide evidence of the presence of horizontal pleiotropy.

CONCLUSIONS

Our findings provided evidence supporting a potential causal relationship between longer telomere length and increased risk of systemic lupus erythematosus.

摘要

目的

探讨端粒长度较短是否是亚洲人群系统性红斑狼疮(SLE)的因果风险因素。

方法

我们应用两样本孟德尔随机化(MR)方法,对 6707 例 SLE 病例和 16047 例对照的全基因组关联研究(GWAS)汇总统计数据进行分析。我们选择了 9 个单核苷酸多态性(SNP)作为端粒长度的全基因组显著工具变量。主要分析采用随机效应逆方差加权(IVW)方法进行。通过 MR-Egger 回归的截距评估水平异质性。

结果

观察到较长的遗传预测端粒长度与系统性红斑狼疮风险增加之间存在潜在的因果关系(OR=1.72,95%CI:1.21,2.46,P=0.01)。MR-Egger 回归显示截距接近零(截距=0.017,P=0.69),这不能提供存在水平异质性的证据。

结论

我们的研究结果提供了证据,支持端粒长度较长与系统性红斑狼疮风险增加之间存在潜在的因果关系。

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