Zhang Hao, Chen Keying, Gao Tongyu, Yan Yu, Liu Ying, Liu Yuxin, Zhu Kexuan, Qi Jike, Zheng Chu, Wang Ting, Zeng Ping
Department of Biostatistics, School of Public Health, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China.
Jiangsu Engineering Research Center of Biological Data Mining and Healthcare Transformation, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China.
NPJ Parkinsons Dis. 2025 Jan 3;11(1):5. doi: 10.1038/s41531-024-00861-5.
The relationship between hearing loss (HL) and Parkinson's disease (PD) remains unclear. Using individual-level and summary-level data from the UK Biobank and the largest genome-wide association studies, we examined this link through observational, Mendelian randomization and genetic pleiotropy analyses. Among 158,229 participants, PD risk rose with HL severity especially in elder and males, and hearing aids significantly reduced PD risk in males. Although our results did not support a causal association, genetic correlation analysis suggested a localized genetic overlap (17q21.31). We identified 1545 SNPs and 63 genes with pleiotropic effects on HL and PD, including 79 novel SNPs across 6 loci, with 3 showing strong co-localization. These loci were enriched in key tissues like brain, heart, liver and pancreas, linked to the dihydrolipoyl dehydrogenase complex pathway, and targeted by drugs such as Warfarin and Phenprocoumon. Overall, this study reveals the risk association, genetic basis, and pleiotropic loci connecting HL and PD.
听力损失（HL）与帕金森病（PD）之间的关系仍不明确。利用英国生物银行的个体水平和汇总水平数据以及最大规模的全基因组关联研究，我们通过观察性、孟德尔随机化和遗传多效性分析来研究这种联系。在158229名参与者中，PD风险随HL严重程度增加而上升，尤其是在老年人和男性中，且助听器显著降低了男性的PD风险。尽管我们的结果不支持因果关联，但遗传相关性分析表明存在局部遗传重叠（17q21.31）。我们确定了1545个单核苷酸多态性（SNP）和63个对HL和PD有多效性影响的基因，包括6个位点的79个新SNP，其中3个显示出强烈的共定位。这些位点在大脑、心脏、肝脏和胰腺等关键组织中富集，与二氢硫辛酰胺脱氢酶复合体途径相关，并受到华法林和苯丙香豆素等药物的靶向作用。总体而言，本研究揭示了连接HL和PD的风险关联、遗传基础和多效性位点。
