端粒长度与听力损失：两样本孟德尔随机化研究。

Telomere Length and Hearing Loss: A Two-Sample Mendelian Randomization.

机构信息

School of Public Health, Hangzhou Normal University, Hangzhou 310000, China.

School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Int J Environ Res Public Health. 2022 Jul 22;19(15):8937. doi: 10.3390/ijerph19158937.

DOI:10.3390/ijerph19158937

PMID:35897312

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9330868/

Abstract

BACKGROUND

Observational studies have suggested that there may be an association between telomere length (TL) and hearing loss (HL). However, inferring causality from observational studies is subject to residual confounding effects, reverse causation, and bias. This study adopted a two-sample Mendelian randomization (MR) approach to evaluate the causal relationship between TL and increased risk of HL.

METHODS

A total of 16 single nucleotide polymorphisms (SNPs) associated with TL were identified from a genome-wide association study (GWAS) meta-analysis of 78,592 European participants and applied to our modeling as instrumental variables. Summary-level data for hearing loss (HL), age-related hearing loss (ARHL), and noise-induced hearing loss (NIHL) were obtained from the recent largest available GWAS and five MR analyses were used to investigate the potential causal association of genetically predicted TL with increased risk for HL, including the inverse-variance-weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode. In addition, sensitivity analysis, pleiotropy, and heterogeneity tests were also used to evaluate the robustness of our findings.

RESULTS

There was no causal association between genetically predicted TL and HL or its subtypes (by the IVW method, HL: odds ratio (OR) = 1.216, = 0.382; ARHL: OR = 0.934, = 0.928; NIHL: OR = 1.003, = 0.776). Although heterogenous sites rs2736176, rs3219104, rs8105767, and rs2302588 were excluded for NIHL, the second MR analysis was consistent with the first analysis (OR = 1.003, = 0.572).

CONCLUSION

There was no clear causal relationship between shorter TLs and increased risk of HL or its subtypes in this dataset.

摘要

背景

观察性研究表明，端粒长度（TL）与听力损失（HL）之间可能存在关联。然而，从观察性研究中推断因果关系受到残余混杂效应、反向因果关系和偏倚的影响。本研究采用两样本孟德尔随机化（MR）方法评估 TL 与 HL 风险增加之间的因果关系。

方法

从 78592 名欧洲参与者的全基因组关联研究（GWAS）荟萃分析中确定了与 TL 相关的 16 个单核苷酸多态性（SNP），并将其作为工具变量应用于我们的模型中。听力损失（HL）、年龄相关性听力损失（ARHL）和噪声性听力损失（NIHL）的汇总水平数据来自最近最大的可用 GWAS，并使用五项 MR 分析来研究遗传预测的 TL 与 HL 风险增加之间的潜在因果关联，包括逆方差加权（IVW）、加权中位数、MR-Egger 回归、简单模式和加权模式。此外，还进行了敏感性分析、多效性和异质性检验，以评估我们研究结果的稳健性。

结果

遗传预测的 TL 与 HL 或其亚型之间没有因果关系（通过 IVW 方法，HL：比值比（OR）= 1.216， = 0.382；ARHL：OR = 0.934， = 0.928；NIHL：OR = 1.003， = 0.776）。尽管排除了 NIHL 的异质位点 rs2736176、rs3219104、rs8105767 和 rs2302588，但第二项 MR 分析与第一项分析一致（OR = 1.003， = 0.572）。