评估肾功能与听力表现之间的因果关系：一项两样本孟德尔随机化研究
Appraising the causal relationship between kidney function and hearing performance: a two-sample Mendelian randomization study.
摘要(中文译文)
流行病学研究报道了慢性肾脏病与听力损伤之间的关联，但其因果关系仍不确定。我们开展了一项双向两样本孟德尔随机化研究，以检验遗传预测的肾功能特征是否因果性地影响言语接受阈，后者是听觉表现的一项客观测量指标。估计肾小球滤过率、慢性肾脏病和血尿素氮的遗传工具来自CKDGen联盟开展的大规模全基因组关联研究，左右耳言语接受阈的汇总统计数据来自英国生物银行。采用逆方差加权法作为主要分析方法，并辅以MR-Egger、加权中位数和基于众数的估计方法。未发现遗传预测的肾功能特征与任一侧耳言语接受阈之间存在稳健的因果关联。血尿素氮、慢性肾脏病和估计肾小球滤过率的逆方差加权估计均不显著（均>0.05）。尽管估计肾小球滤过率与左耳言语接受阈的逆方差加权估计接近名义显著性，且部分次要分析显示名义关联，但这些发现在各方法之间不一致，未达到我们进行稳健因果推断的标准。反向孟德尔随机化分析也未显示显著关联。敏感性分析未发现存在方向性水平多效性的证据，且离群值校正未实质性改变结果。本研究未提供稳健的遗传学证据支持在当前孟德尔随机化框架下，遗传预测的肾功能特征与以言语接受阈测量的听力功能之间在任何方向上存在因果关系。所观察到的流行病学关联可能反而反映了共同的全身性、发育性或环境机制。
Abstract
Epidemiological studies have reported an association between chronic kidney disease and hearing impairment, but the causal relationship remains uncertain. We conducted a bidirectional two-sample Mendelian randomization study to examine whether genetically predicted kidney function traits causally influence speech reception threshold, an objective measure of auditory performance. Genetic instruments for estimated glomerular filtration rate, chronic kidney disease, and blood urea nitrogen were obtained from large-scale genome-wide association studies conducted by the CKDGen Consortium, and summary statistics for speech reception threshold in the left and right ears were derived from the UK Biobank. The inverse variance weighted method was used as the primary analytical approach, complemented by MR-Egger, weighted median, and mode-based estimators. No robust causal associations were identified between genetically predicted kidney function traits and SRT in either ear. IVW estimates for BUN, CKD, and eGFR were non-significant (all > 0.05). Although the IVW estimate for eGFR and left-ear SRT approached nominal significance and some secondary analyses showed nominal associations, these findings were inconsistent across methods and did not meet our criteria for robust causal inference. Reverse Mendelian randomization analyses also showed no significant associations. Sensitivity analyses showed no evidence of directional horizontal pleiotropy, and outlier correction did not materially change the results. This study provides no robust genetic evidence supporting a causal relationship between genetically predicted kidney function traits and hearing function, as measured by speech reception threshold, in either direction under the current MR framework. The observed epidemiological association may instead reflect shared systemic, developmental, or environmental mechanisms.
如何引用
AMA
Weiling Huang, Zhao Li, Yue Zhang, Hongsheng Tan, Jianrong Shi. Appraising the causal relationship between kidney function and hearing performance: a two-sample Mendelian randomization study.. Renal failure. 2026; doi:10.1080/0886022X.2026.2663653.
APA
Weiling Huang, Zhao Li, Yue Zhang, Hongsheng Tan, Jianrong Shi (2026). Appraising the causal relationship between kidney function and hearing performance: a two-sample Mendelian randomization study.. Renal failure. https://doi.org/10.1080/0886022X.2026.2663653
GB/T 7714
Weiling Huang, Zhao Li, Yue Zhang, Hongsheng Tan, Jianrong Shi. Appraising the causal relationship between kidney function and hearing performance: a two-sample Mendelian randomization study.[J]. Renal failure, 2026 doi:10.1080/0886022X.2026.2663653.
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