睡眠特征与血清尿酸水平的因果效应：一项双向孟德尔随机化研究

doi:10.12114/j.issn.1007-9572.2025.0353

中国全科医学 ›› 2026, Vol. 29 ›› Issue (17): 2354-2360.DOI: 10.12114/j.issn.1007-9572.2025.0353

睡眠特征与血清尿酸水平的因果效应：一项双向孟德尔随机化研究

张馨文¹, 魏光成², 张解玉², 石金杰¹, 李晓旭², 马锐¹, 押玉珑¹, 彭九程¹, 曹炜²^,^*()

1．100029　北京市，北京中医药大学
2．100102　北京市，中国中医科学院望京医院风湿科

收稿日期:2025-09-10 修回日期:2025-12-10 出版日期:2026-06-15 发布日期:2026-05-21
通讯作者: 曹炜
作者贡献：
张馨文负责文章的构思与设计、统计学处理、结果的分析与解释、论文撰写；张馨文、魏光成、张解玉负责图、表的绘制与展示；石金杰、李晓旭、马锐负责论文的修订；押玉珑、彭九程负责数据的收集与整理；曹炜负责文章的质量控制及审校，对文章整体负责。
基金资助:
国家重点研发计划(2022YFC3501201)

The Causal Relationship between Sleep Patterns and Serum Uric Acid: a Bidirectional Mendelian Randomization Study

ZHANG Xinwen¹, WEI Guangcheng², ZHANG Xieyu², SHI Jinjie¹, LI Xiaoxu², MA Rui¹, YA Yulong¹, PENG Jiucheng¹, CAO Wei²^,^*()

1. Beijing University of Chinese Medicine, Beijing 100029, China
2. Department of Rheumatology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China

Received:2025-09-10 Revised:2025-12-10 Published:2026-06-15 Online:2026-05-21
Contact: CAO Wei

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摘要/Abstract

摘要： 背景高尿酸血症（HUA）是全球性健康问题，其患病率在中国呈上升趋势。睡眠作为重要的生活方式因素，其与血清尿酸（SUA）水平的关系在既往观察性研究中结论不一，二者间的因果关系尚不明确。因此，有必要采用更可靠的方法阐明其内在关联。目的利用双向孟德尔随机化（MR）方法，探究睡眠时长、日间小睡频率与SUA水平之间的双向因果关系。方法本研究基于大规模全基因组关联研究（GWAS）的公开汇总数据，睡眠时长（n=127 573）、日间小睡频率（n=452 633）及SUA水平（n=288 649）的数据均来自欧洲人群。采用双向两样本MR设计，筛选符合条件的单核苷酸多态性（SNP）作为工具变量。采用反方差加权（IVW）法、MR-Egger回归、加权中位数法及MR-PRESSO法评估因果效应，并采用异质性检验、逐一排除法检验等进行敏感性分析以验证结果的稳健性。结果 MR分析结果显示，遗传预测的睡眠时长与SUA水平呈负向因果关联（OR=0.81，95%CI=0.67~0.98，P=0.03）；遗传预测的日间小睡频率与SUA水平呈正向因果关联（OR=1.20，95%CI=1.05~1.37，P=0.009）。反向MR分析未发现SUA水平对睡眠时长或日间小睡频率有因果影响（P>0.05）。敏感性分析未发现明显的水平多效性，结果稳健。结论本研究从遗传学层面证实，较短的睡眠时长和较高的日间小睡频率是导致SUA水平升高的独立危险因素。改善睡眠习惯可能成为预防和管理HUA的有效非药物干预策略。

关键词: 高尿酸血症, 血清尿酸, 睡眠时长, 日间小睡, 因果推断, 双向孟德尔随机化

Abstract:

Background

Hyperuricemia (HUA) is a global health concern, with its prevalence on the rise in China. Sleep, as an important lifestyle factor, shows an inconsistent relationship with serum uric acid (SUA) levels in previous observational studies, and the causal relationship between them remains unclear. Therefore, it is necessary to employ more reliable methods to clarify their intrinsic association.

Objective

To investigate the bidirectional causal relationships between sleep duration, daytime napping frequency, and SUA levels using a bidirectional Mendelian randomization (MR) approach.

Methods

This study was based on publicly available summary data from large-scale genome-wide association studies (GWAS). Data on sleep duration (n=127 573), daytime napping frequency (n=452 633), and SUA levels (n=288 649) were derived from European populations. A bidirectional two-sample MR design was employed, screening eligible single nucleotide polymorphisms (SNPs) as instrumental variables. The inverse variance weighted (IVW) method, MR-Egger regression, weighted median method, and MR-PRESSO method were used to assess causal effects. Sensitivity analyses, including heterogeneity tests and leave-one-out analysis, were conducted to verify the robustness of the results.

Results

The MR analysis results showed that the genetic prediction of sleep duration was a negative causal relationship with the SUA level (OR=0.81, 95%CI=0.67-0.98, P=0.03), while the frequency of daytime naps predicted by genetics has a positive causal relationship with the level of SUA (OR=1.20, 95%CI=1.05-1.37, P=0.009). Reverse MR analysis found no causal effect of SUA levels on either sleep duration or daytime napping frequency (P>0.05). Sensitivity analyses detected no significant horizontal pleiotropy, indicating robust findings.

Conclusion

This study provides genetic evidence that shorter sleep duration and higher daytime napping frequency are independent risk factors for elevated SUA levels. Improving sleep habits may serve as an effective non-pharmacological intervention strategy for the prevention and management of HUA.

Key words: Hyperuricacidemia, Serum uric acid, Sleep duration, Daytime napping, Causal inference, Bidirectional Mendelian randomization

中图分类号:

R 259

张馨文,魏光成,张解玉,等. 睡眠特征与血清尿酸水平的因果效应：一项双向孟德尔随机化研究[J]. 中国全科医学, 2026, 29(17): 2354-2360. DOI: 10.12114/j.issn.1007-9572.2025.0353.
ZHANG Xinwen,WEI Guangcheng,ZHANG Xieyu, et al. The Causal Relationship between Sleep Patterns and Serum Uric Acid: a Bidirectional Mendelian Randomization Study[J]. Chinese General Practice, 2026, 29(17): 2354-2360. DOI: 10.12114/j.issn.1007-9572.2025.0353.

图/表 5

图1 孟德尔随机化分析流程注：SNP=单核苷酸多态性。

Figure 1 Flowchart of the Mendelian randomization analysis

图2 睡眠时长对尿酸水平因果估计的森林图

Figure 2 Forest plot of the causal estimate of sleep duration on SUA levels

图3 尿酸水平对睡眠时长的因果估计森林图

Figure 3 Forest plot of the causal estimate of SUA levels on sleep duration

图4 日间小睡频率对尿酸水平因果估计的森林图

Figure 4 Forest plot of the causal estimate of daytime napping frequency on SUA levels

图5 尿酸水平对日间小睡频率的因果估计森林图

Figure 5 Forest plot of the causal estimate of SUA levels on daytime napping frequency

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睡眠特征与血清尿酸水平的因果效应：一项双向孟德尔随机化研究

The Causal Relationship between Sleep Patterns and Serum Uric Acid: a Bidirectional Mendelian Randomization Study

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