{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:13:22Z","timestamp":1760058802332,"version":"build-2065373602"},"reference-count":70,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T00:00:00Z","timestamp":1745625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovation Fund Project of the Gansu Provincial Department of Education","award":["2024B-104","2023-ZD-238"],"award-info":[{"award-number":["2024B-104","2023-ZD-238"]}]},{"name":"Lanzhou Science and Technology Plan Project","award":["2024B-104","2023-ZD-238"],"award-info":[{"award-number":["2024B-104","2023-ZD-238"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Radiotherapy-induced hearing impairment significantly affects patients\u2019 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\u2013protein 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.<\/jats:p>","DOI":"10.3390\/ijms26094132","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T11:48:33Z","timestamp":1745840913000},"page":"4132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Risk Loci for Radiotherapy-Induced Tinnitus and Hearing Loss Through Integrated Genomic Analysis"],"prefix":"10.3390","volume":"26","author":[{"given":"Fan","family":"Ding","sequence":"first","affiliation":[{"name":"Teaching and Experimental Training Center, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zehao","family":"Pang","sequence":"additional","affiliation":[{"name":"Teaching and Experimental Training Center, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiujia","family":"Ji","sequence":"additional","affiliation":[{"name":"Teaching and Experimental Training Center, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanfang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Teaching and Experimental Training Center, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiulan","family":"Wang","sequence":"additional","affiliation":[{"name":"Teaching and Experimental Training Center, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6302-8612","authenticated-orcid":false,"given":"Zhitong","family":"Bing","sequence":"additional","affiliation":[{"name":"Advanced Nuclear Physics Laboratory, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1093\/neuonc\/noae160","article-title":"The emerging field of viroimmunotherapy for pediatric brain tumors","volume":"26","author":"Laspidea","year":"2024","journal-title":"Neuro-Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"DeNunzio, N.J., and Yock, T.I. 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