听力损失与帕金森病风险无关：一项孟德尔随机化研究。
Hearing loss is not associated with risk of Parkinson's disease: A Mendelian randomization study.
作者信息
Ning Pingping, Mu Xin, Guo Xingzhi, Li Rui
机构信息
Department of Geriatric Neurology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
Shaanxi Provincial Clinical Research Center for Geriatric Medicine, Xi'an, 710068, China.
出版信息
Heliyon. 2024 Jun 6;10(11):e32533. doi: 10.1016/j.heliyon.2024.e32533. eCollection 2024 Jun 15.
PURPOSE
A few observational studies have indicated that Parkinson's disease (PD) risk may be higher in those with hearing loss, but the two's causal relationship is yet unknown. Using Mendelian randomization (MR) methods, this study sought to explore the causal link between hearing loss and the risk of PD.
METHODS
We identified single nucleotide polymorphisms (SNPs) linked to hearing loss (-value<5E-08) in a genome-wide association study (GWAS) included 323,978 people from the UK Biobank. The summary data for PD in the discovery group came from a GWAS meta-analysis of 33,647 cases and 449,056 healthy participants of European descent. Using summary data from the aforementioned GWAS of PD (N = 33,647) and hearing loss (N = 323,978), we carried out a two-sample MR study. As validation groups, two separate PD GWAS studies were used. Inverse variance weighting (IVW) was utilized in the principal MR analysis. For our findings to be reliable, further analyses were carried out with the Cochran's Q test, MR-Egger intercept, and leave-one-out analysis. In addition, we assessed the causal link between various forms of hearing loss and PD using the IVW approach.
RESULTS
Twenty-two SNPs with genome-wide significance linked to hearing loss were used as instrumental factors. In the discovery dataset, we failed to detect a causal relationship between hearing loss and PD (OR = 1.297; 95 % CI = 0.420-4.007; -value = 0.651). The findings of other methods agreed with the IVW method. The results were robust under sensitivity analyses. Furthermore, the above findings were confirmed in two validation PD datasets. Additionally, no causal correlation was found between genetic prediction of four different types of hearing loss and PD (conductive hearing loss, IVW: OR = 1.058, 95%CI = 0.988-1.133, -value = 0.108; sudden idiopathic hearing loss, IVW: OR = 0.936, 95%CI = 0.863-1.016, -value = 0.113; mixed conductive and sensorineural hearing loss, IVW: OR = 0.963, 95%CI = 0.878-1.058, -value = 0.436; sensorineural hearing loss, IVW: OR = 1.050, 95%CI = 0.948-1.161, -value = 0.354).
CONCLUSION
In those of European heritage, our investigation revealed no causal link between hearing loss and PD risk.
目的
一些观察性研究表明，听力损失患者患帕金森病（PD）的风险可能更高，但两者之间的因果关系尚不清楚。本研究采用孟德尔随机化（MR）方法，旨在探讨听力损失与PD风险之间的因果联系。
方法
我们在一项全基因组关联研究（GWAS）中确定了与听力损失相关的单核苷酸多态性（SNP，P值<5E-08），该研究纳入了英国生物银行的323,978人。发现组中PD的汇总数据来自对33,647例病例和449,056名欧洲血统健康参与者的GWAS荟萃分析。利用上述PD（N = 33,647）和听力损失（N = 323,978）的GWAS汇总数据，我们进行了两样本MR研究。作为验证组，使用了两项独立的PD GWAS研究。主要MR分析采用逆方差加权（IVW）法。为确保研究结果可靠，我们还使用 Cochr an's Q检验、MR-Egger截距和留一法进行了进一步分析。此外，我们采用IVW方法评估了各种形式的听力损失与PD之间的因果联系。
结果
22个具有全基因组意义的与听力损失相关的SNP被用作工具因子。在发现数据集中，我们未检测到听力损失与PD之间的因果关系（OR = 1.297；95%CI = 0.420 - 4.007；P值 = 0.651）。其他方法的结果与IVW方法一致。在敏感性分析中，结果具有稳健性。此外，上述结果在两个验证性PD数据集中得到了证实。此外，在四种不同类型听力损失的遗传预测与PD之间未发现因果相关性（传导性听力损失，IVW：OR = 1.058，95%CI = 0.988 - 1.133，P值 = 0.108；特发性突发性感音神经性听力损失，IVW：OR = 0.936，95%CI = 0.863 - 1.016，P值 = 0.113；混合性传导性和感音神经性听力损失，IVW：OR = 0.963，95%CI = 0.878 - 1.058，P值 = 0.436；感音神经性听力损失，IVW：OR = 1.050，95%CI = 0.948 - 1.161，P值 = 0.354）。
结论
在欧洲血统人群中，我们的研究未发现听力损失与PD风险之间存在因果联系。
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