An exploratory Mendelian randomization study on the genetically predicted effects of circulating blood cells on osteoarthritis risk

IF 2.4 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics Pub Date : 2026-01-01 Epub Date: 2026-04-17 DOI:10.1016/j.clinsp.2026.100959

Lei Zhou, Jialin Jia, Xingren Chen, Tong Chen

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引用次数: 0

Abstract

Background

The causal relationship between circulating blood cells and Osteoarthritis (OA) remains unclear. This study aimed to explore this potential relationship using a two-sample Mendelian Randomization (MR) approach.

Methods

Data from large-scale GWAS (Blood Cell Consortium and GWAS Catalog) were analyzed using two-sample MR methods, with Inverse Variance Weighting as the primary approach. A Bonferroni correction was applied for multiple testing for the two primary traits. Robustness was assessed through comprehensive sensitivity analyses for heterogeneity and pleiotropy.

Results

After Bonferroni correction, Genetically Predicted Hemoglobin (HGB) showed a weak genetic association consistent with a potential causal pathway for OA risk (OR = 1.004, 95% CI 1.001–1.007, p = 0.018). The association for Neutrophil (NEU) count was not statistically significant. While sensitivity analyses did not detect directional pleiotropy, significant heterogeneity was observed for the genetic instruments.

Conclusion

This exploratory study provides preliminary genetic evidence for a statistically significant but clinically negligible MR estimate of hemoglobin in OA pathogenesis. The clinical and biological significance of this minuscule effect remains uncertain. The findings should be interpreted as hypothesis-generating, highlighting the need for further research rather than establishing a definitive causal link.

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一项关于循环血细胞对骨关节炎风险的遗传预测作用的探索性孟德尔随机化研究

背景循环血细胞与骨关节炎（OA）之间的因果关系尚不清楚。本研究旨在利用双样本孟德尔随机化（MR）方法探讨这种潜在的关系。方法采用双样本MR方法对大型GWAS （Blood Cell Consortium和GWAS Catalog）的数据进行分析，方差逆加权为主要方法。采用Bonferroni校正对两个主要性状进行多重检验。通过对异质性和多效性的综合敏感性分析来评估稳健性。结果经Bonferroni校正后，遗传预测血红蛋白（HGB）显示出弱遗传关联，与OA风险的潜在因果途径一致（OR = 1.004, 95% CI 1.001-1.007, p = 0.018）。中性粒细胞（NEU）计数的相关性无统计学意义。虽然敏感性分析没有检测到定向多效性，但在遗传工具中观察到显著的异质性。结论：这项探索性研究为OA发病机制中血红蛋白的MR估计提供了初步的遗传学证据，但在临床上可忽略不计。这种微小影响的临床和生物学意义尚不确定。这些发现应该被解释为产生假设，强调需要进一步研究，而不是建立明确的因果关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinics 医学-医学：内科

CiteScore

4.10

自引率

3.70%

发文量

129

审稿时长

52 days

期刊介绍： CLINICS is an electronic journal that publishes peer-reviewed articles in continuous flow, of interest to clinicians and researchers in the medical sciences. CLINICS complies with the policies of funding agencies which request or require deposition of the published articles that they fund into publicly available databases. CLINICS supports the position of the International Committee of Medical Journal Editors (ICMJE) on trial registration.