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睡眠特征与终末期肾病风险:一项孟德尔随机化研究。

Sleep traits and risk of end-stage renal disease: a mendelian randomization study.

机构信息

Department of Nephrology, Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China.

General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

出版信息

BMC Med Genomics. 2023 Apr 7;16(1):76. doi: 10.1186/s12920-023-01497-9.

Abstract

BACKGROUND

Epidemiological evidence relating sleep disorders to end-stage renal disease (ESRD) has been obscure. The present study is sought to examine the association between sleep traits and ESRD.

METHODS

For this analysis, we selected genetic instruments for sleep traits from published genome-wide association studies (GWAS). As instrumental variables, independent genetic variations linked with seven sleep-related features (sleep duration, getting up in the morning, daytime napping, chronotype of morning/evening person, sleeplessness/insomnia, non-snoring, and daytime dozing) were chosen. A two-sample Mendelian randomization (TSMR) study was conducted to assess the causal relationship between sleep traits and ESRD (N = 33,061). The reverse MR analysis subsequently determined the causal relationship between ESRD and sleep traits. The causal effects were estimated using inverse variance weighted, MR-Egger, weighted median. To conduct sensitivity studies, Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plot were used. To study the potential mediators, multivariable mendelian randomization analyses were undertaken further.

RESULTS

Genetically predicted sleeplessness/ insomnia (OR = 6.11, 95%CI 1.00-37.3, P = 0.049, FDR = 0.105), getting up in the morning easily(OR = 0.23, 95%CI 0.063-0.85; P = 0.0278, FDR = 0.105), non-snoring (OR = 4.76E-02, 95%CI 2.29E-03-0.985, P = 0.0488, FDR = 0.105) was suggestively associated with the risk of ESRD. However, we found no evidence favoring a causal association between other sleep traits and ESRD through the IVW method.

CONCLUSION

The present TSMR found no strong evidence of a bidirectional causal association between genetically predicted sleep traits and ESRD.

摘要

背景

睡眠障碍与终末期肾病(ESRD)之间的流行病学证据尚不清楚。本研究旨在探讨睡眠特征与 ESRD 之间的关系。

方法

在这项分析中,我们从已发表的全基因组关联研究(GWAS)中选择了与睡眠特征相关的遗传工具。作为工具变量,我们选择了与七种与睡眠相关的特征(睡眠时间、早上起床、白天小睡、晨型/晚型、失眠/入睡困难、不打鼾和白天瞌睡)相关的独立遗传变异。进行了两样本 Mendelian 随机化(TSMR)研究,以评估睡眠特征与 ESRD 之间的因果关系(N=33061)。随后进行了反向 MR 分析,以确定 ESRD 与睡眠特征之间的因果关系。使用逆方差加权、MR-Egger、加权中位数估计因果效应。为了进行敏感性研究,使用 Cochran's Q 检验、MR-Egger 截距检验、MR-PRESSO、逐一剔除分析和漏斗图。为了研究潜在的中介物,进一步进行了多变量 Mendelian 随机化分析。

结果

遗传预测的失眠/入睡困难(OR=6.11,95%CI 1.00-37.3,P=0.049,FDR=0.105)、易晨起(OR=0.23,95%CI 0.063-0.85;P=0.0278,FDR=0.105)、不打鼾(OR=4.76E-02,95%CI 2.29E-03-0.985,P=0.0488,FDR=0.105)与 ESRD 的风险呈显著相关。然而,我们通过 IVW 方法没有发现其他睡眠特征与 ESRD 之间存在因果关系的证据。

结论

本 TSMR 没有发现遗传预测的睡眠特征与 ESRD 之间存在双向因果关系的有力证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/10080763/e14c6bd7708f/12920_2023_1497_Figd_HTML.jpg

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