Yu Jie, Zhu Jingjing, Zhong Hua, Zhang Zicheng, Liu Jiawen, Lin Xin, Zeng Guanghua, Zhang Min, Wu Chong, Deng Youping, Sun Yanfa, Wu Lang
College of Life Science, Fujian Provincial Key Laboratory for the Prevention and Control of Animal Infectious Diseases and Biotechnology, Fujian Provincial Universities Key Laboratory of Preventive Veterinary Medicine and Biotechnology (Longyan University), Longyan University, Longyan, P. R. China.
Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.
OMICS. 2024 Dec;28(12):620-631. doi: 10.1089/omi.2024.0172. Epub 2024 Nov 25.
Age-related hearing impairment (ARHI) is a major planetary health burden that is in need of precision medicine for prevention, diagnosis, and treatment. The present study was set out to identify candidate epigenetic markers for ARHI. Associations of genetically predicted DNA methylation levels with ARHI risk were evaluated using two sets of blood DNA methylation genetic prediction models in 147,997 cases and 575,269 controls of European descent. A total of 1314 CpG sites (CpGs) were significantly associated with ARHI risk at a false discovery rate (FDR) <0.05, including 12 putatively causal CpGs based on fine-mapping analysis. Measured methylation levels of 247 of the associated CpGs were significantly correlated with measured expression levels of 127 nearby genes in blood at an FDR <0.05. A total of 37 CpGs and their 18 nearby genes showed consistent association directions for the methylation-gene expression-ARHI risk pathway. Importantly, three genes (, , and ) were enriched in auditory disease categories. Our results indicate that specific CpGs may modulate ARHI risk by regulating the expression of candidate ARHI target genes. Future precision medicine and biomarker development research on ARHI are called for.
年龄相关性听力减退（ARHI）是一项重大的全球健康负担，需要精准医学来进行预防、诊断和治疗。本研究旨在确定ARHI的候选表观遗传标记。在147,997例欧洲血统病例和575,269例对照中，使用两组血液DNA甲基化遗传预测模型评估了基因预测的DNA甲基化水平与ARHI风险的关联。共有1314个CpG位点（CpGs）在错误发现率（FDR）<0.05时与ARHI风险显著相关，其中包括基于精细定位分析的12个推定因果CpGs。在FDR<0.05时测定的247个相关CpGs的甲基化水平与血液中127个附近基因的测定表达水平显著相关。共有37个CpGs及其18个附近基因在甲基化-基因表达-ARHI风险途径中显示出一致的关联方向。重要的是，三个基因（、和）在听觉疾病类别中富集。我们的结果表明，特定的CpGs可能通过调节候选ARHI靶基因的表达来调节ARHI风险。未来需要开展针对ARHI的精准医学和生物标志物开发研究。
