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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Neuro-Otology
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1422241

Investigating the Causal Relationship Between Inflammation and Multiple Types of Hearing Loss: A Multi-Omics Approach Combining Mendelian Randomization and Molecular Docking

Provisionally accepted
Jingqi Zhang Jingqi Zhang 1Tao Guo Tao Guo 1Yaxin Chen Yaxin Chen 1Xiangjin Wang Xiangjin Wang 2Lijiao Wu Lijiao Wu 1Hui Xie Hui Xie 1*
  • 1 Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
  • 2 School of Sports Medicine and Health, Chengdu Sport University, Chengdu, Sichuan Province, China

The final, formatted version of the article will be published soon.

    Background: Hearing loss affects over 10% of the global population. Inflammation is a key factor in hearing loss caused by noise, infection, and aging, damaging various hearing-related tissues (e.g., spiral ligament, stria vascularis). Mendelian randomization (MR) can help identify potential causal relationships and therapeutic targets.We conducted MR analyses on 91 inflammatory proteins (n=14,824) and genome-wide association study results for various hearing loss types in European ancestry populations, including sensorineural hearing loss (SNHL; ncases=15,952, ncontrols=196,592), sudden idiopathic hearing loss (SIHL; ncases=1,491, ncontrols=196,592), and other hearing loss (OHL; ncases=4,157, ncontrols=196,592). Additionally, hearing loss with difficulty in hearing (ncases=14,654, ncontrols=474,839) served as a validation set. To predict inflammatory protein-enriched pathways and tissues, we performed enrichment analysis, functional annotation, and tissue analyses using "OmicsNet2.0" and "FUMA" platforms. We also combined "CoreMine" and molecular docking to explore potential drugs targeting inflammatory proteins and investigate binding efficacy.Results: CCL19 was identified as a common risk factor for SNHL and OHL, which was validated in the hearing loss with difficulty in hearing dataset. Tissue analysis revealed that SIHL-related inflammatory proteins were enriched in the amygdala. Multi-omics research indicated associations between inflammatory proteins and neurodegenerative diseases. Molecular docking studies suggested that Chuanxiong Rhizoma and Uncariae Ramulus Cumuncis are potential drugs for targeting CCL19.This study identified CCL19 as a common risk factor for various types of hearing loss through MR analysis, highlighting the crucial role of inflammatory proteins in hearing loss. The enrichment of related inflammatory proteins in the amygdala and their association with neurodegenerative diseases provide new insights into the mechanisms of hearing loss.

    Keywords: sensorineural hearing loss, Sudden idiopathic hearing loss, Mendelian randomization, Inflammation, multi-omics

    Received: 23 Apr 2024; Accepted: 08 Nov 2024.

    Copyright: © 2024 Zhang, Guo, Chen, Wang, Wu and Xie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hui Xie, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.