The non-causative role of abnormal serum uric acid in intervertebral disc degeneration: A Mendelian randomization study

IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine Pub Date : 2023-09-29 DOI:10.1002/jsp2.1283
Yang-Ting Cai, Yong-Xian Li, Li-Ren Wang, Ling Mo, Ying Li, Shun-Cong Zhang
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Abstract

Background

Intervertebral disc degeneration (IDD) is a common musculoskeletal disorder that contributes significantly to disability and healthcare costs. Serum urate concentration has been implicated in the development of various musculoskeletal conditions. While previous observational studies have suggested an association between the two conditions, it might confound the effect of serum urate concentrations on IDD. This Mendelian randomization (MR) study aimed to investigate the causal relationship between serum urate concentration and IDD.

Methods

We performed a two-sample MR analysis using summary-level data from genome-wide association studies (GWAS) of serum urate concentration (n = 13 585 994 European ancestry) and IDD (n = 16 380 337 European ancestry). Single nucleotide polymorphisms (SNPs) significantly associated with serum urate concentration (p < 5 × 10−8) were selected as instrumental variables. The associations between genetically predicted serum urate concentration and IDD were estimated using the inverse-variance weighted (IVW) method, with sensitivity analyses employing the weighted median, MR-Egger, and MR-PRESSO approaches to assess the robustness of the findings.

Results

In the primary IVW analysis, genetically predicted serum urate concentration was unrelated associated with IDD (odds ratio [OR] = 1.00, 95% confidence interval (CI): 1.00–1.00, p = 0.17)). The results remained consistent across the sensitivity analyses, and no significant directional pleiotropy was detected (MR-Egger intercept: p = 0.15).

Conclusions

This MR study provides evidence that there is no causal relationship between serum urate concentration and IDD. It suggests previous observational associations may be confounded. Serum urate levels are unlikely to be an important contributor to IDD.

Abstract Image

血清尿酸异常在椎间盘退变中的非诱因作用:孟德尔随机研究
背景 椎间盘退行性变(IDD)是一种常见的肌肉骨骼疾病,严重导致残疾和医疗费用的增加。血清尿酸盐浓度与各种肌肉骨骼疾病的发病有关。虽然之前的观察性研究表明这两种疾病之间存在关联,但这可能会混淆血清尿酸盐浓度对 IDD 的影响。这项孟德尔随机化(MR)研究旨在调查血清尿酸盐浓度与 IDD 之间的因果关系。 方法 我们利用血清尿酸盐浓度(n = 13 585 994 欧洲血统)和 IDD(n = 16 380 337 欧洲血统)全基因组关联研究(GWAS)的汇总数据进行了双样本 MR 分析。研究人员选择了与血清尿酸盐浓度(p < 5 × 10-8)显著相关的单核苷酸多态性(SNPs)作为工具变量。采用逆方差加权法(IVW)估计了遗传预测血清尿酸盐浓度与 IDD 之间的关联,并采用加权中位数法、MR-Egger 法和 MR-PRESSO 法进行了敏感性分析,以评估研究结果的稳健性。 结果 在主要的 IVW 分析中,遗传预测的血清尿酸盐浓度与 IDD 无关(比值比 [OR] = 1.00,95% 置信区间 (CI):1.00-1.00,p = 0.17))。敏感性分析的结果保持一致,未发现明显的方向性多效性(MR-Egger 截距:P = 0.15)。 结论 这项 MR 研究提供了血清尿酸盐浓度与 IDD 之间不存在因果关系的证据。它表明以前的观察性关联可能被混淆了。血清尿酸盐浓度不太可能是导致 IDD 的重要因素。
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来源期刊
JOR Spine
JOR Spine ORTHOPEDICS-
CiteScore
6.40
自引率
18.90%
发文量
42
审稿时长
10 weeks
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