文献类型：期刊文献

英文题名：Identification of Risk Loci for Radiotherapy-Induced Tinnitus and Hearing Loss Through Integrated Genomic Analysis

作者：Ding, Fan[1];Pang, Zehao[1];Ji, Xiujia[1];Jiang, Yuanfang[1];Wang, Qiulan[1];Bing, Zhitong[2]

第一作者：丁繁

通信作者：Ding, F[1];Bing, ZT[2]

机构：[1]Gansu Univ Chinese Med, Teaching & Expt Training Ctr, Lanzhou 730000, Peoples R China;[2]Chinese Acad Sci, Inst Modern Phys, Adv Nucl Phys Lab, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Teaching & Expt Training Ctr, Lanzhou 730000, Peoples R China;[2]corresponding author), Chinese Acad Sci, Inst Modern Phys, Adv Nucl Phys Lab, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

卷号：26

期号：9

外文期刊名：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

收录：;Scopus(收录号：2-s2.0-105004886321);WOS:【SCI-EXPANDED(收录号:WOS:001486459500001)】；

基金：This study was supported by the Innovation Fund Project of the Gansu Provincial Department of Education (Grant ID: 2024B-104) and the Lanzhou Science and Technology Plan Project (Grant ID: 2023-ZD-238).

语种：英文

外文关键词：radiotherapy; tinnitus; hearing loss; genetic variants; PheWAS

摘要：Radiotherapy-induced hearing impairment significantly affects patients' quality of life, yet its genetic basis remains poorly understood. This study seeks to identify genetic variants associated with radiotherapy-induced tinnitus and hearing loss and explore their functional implications. A genome-wide association study (GWAS) was conducted to identify single-nucleotide polymorphisms (SNPs) associated with radiotherapy-induced tinnitus and hearing loss. Protein-protein interaction networks and functional enrichment analyses were performed to explore underlying biological pathways. A phenome-wide association study (PheWAS) analysis across five databases examined associations between identified SNPs and various phenotypes. The GWAS identified 97 SNPs significantly associated with radiotherapy-induced tinnitus and 76 SNPs with hearing loss. Tinnitus-associated variants were enriched in pathways involving Wnt signaling and telomerase RNA regulation, while hearing-loss-associated variants were linked to calcium-dependent cell adhesion and neurotransmitter receptor regulation. The PheWAS analysis revealed significant associations between these hearing-impairment-related SNPs and metabolic phenotypes, particularly BMI and metabolic disorders. A chromosomal distribution analysis showed concentrated significant SNPs on chromosomes 1, 2, 5, and 10. This study identified distinct genetic architectures underlying radiotherapy-induced tinnitus and hearing loss, revealing different molecular pathways involved in their pathogenesis. The unexpected association with metabolic phenotypes suggests potential interactions between metabolic status and susceptibility to radiotherapy-induced hearing complications. These findings provide insights for developing genetic screening tools and targeted interventions to prevent or mitigate radiotherapy-related hearing damage.