Investigating sex-specific associations of Parkinson's disease with sex hormones and sex hormones-related phenotypes using Mendelian randomization

IF 3.1 3区医学 Q2 CLINICAL NEUROLOGY

Parkinsonism & related disorders Pub Date : 2025-04-08 DOI:10.1016/j.parkreldis.2025.107831

Shulin Liu , Yuxuan Hu , Jiabin Liu , Yang Luo , Taole Li , Zhenhua Liu , Qian Xu , Qiying Sun , Xinxiang Yan , Jinchen Li , Beisha Tang , Zhihui Tan , Jifeng Guo

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引用次数: 0

Abstract

Background

It has been reported that the incidence of Parkinson's disease (PD) in men is 1.5 times that of women, which is easily associated with the protective effect of estrogens on the dopaminergic system. However, the exact direction and magnitude of the effect of sex hormones on PD risk have not been clarified. This study aimed to evaluate the sex-specific association between PD and sex hormones and their related phenotypes using Mendelian randomization (MR).

Method

We utilized summary statistics from seven sex-specific genome-wide association studies (GWAS), including the UK Biobank, FinnGen, the INTERVAL Study, and the International Parkinson's Disease Genomics Consortium. Using univariable MR (UVMR) and multivariable MR (MVMR), we investigated causal relationships between genetically predicted sex hormone levels and PD, as well as sex hormone-related traits.

Result

We found a negative genetic correlation between PD and total testosterone levels (rg = −0.019, p = 0.046) and bioavailable testosterone levels (rg = −0.028, p = 0.019) among the entire population. UVMR results suggested that genetically predicted elevated bioavailable and total testosterone levels were associated with a reduced risk of PD in the entire population. When evaluating reverse causation, we found that genetically predicted female PD was associated with lower levels of sex hormone-binding globulin. Using MVMR, we further identified a suggestive association between genetically predicted total testosterone levels and a lower risk of PD.

Conclusion

Based on our findings, we believe that there may be a potential association between genetically determined testosterone levels and the risk of PD.

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背景据报道，男性帕金森病（PD）的发病率是女性的 1.5 倍，这很容易与雌激素对多巴胺能系统的保护作用有关。然而，性激素对帕金森病风险影响的确切方向和程度尚未明确。本研究旨在利用孟德尔随机法（MR）评估帕金森病与性激素及其相关表型之间的性别特异性关联。方法我们利用了英国生物库、FinnGen、INTERVAL 研究和国际帕金森病基因组学联合会等七项性别特异性全基因组关联研究（GWAS）的汇总统计数据。结果我们发现，在整个人群中，帕金森病与总睾酮水平（rg = -0.019，p = 0.046）和生物可用睾酮水平（rg = -0.028，p = 0.019）之间存在负遗传相关性。UVMR 的结果表明，遗传预测的生物可用睾酮和总睾酮水平升高与整个人群患帕金森病的风险降低有关。在评估反向因果关系时，我们发现从遗传学角度预测的女性帕金森病与较低的性激素结合球蛋白水平有关。结论根据我们的研究结果，我们认为基因决定的睾酮水平与罹患帕金森病的风险之间可能存在潜在的关联。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Parkinsonism & related disorders 医学-临床神经学

CiteScore

6.20

自引率

4.90%

发文量

292

审稿时长

39 days

期刊介绍： Parkinsonism & Related Disorders publishes the results of basic and clinical research contributing to the understanding, diagnosis and treatment of all neurodegenerative syndromes in which Parkinsonism, Essential Tremor or related movement disorders may be a feature. Regular features will include: Review Articles, Point of View articles, Full-length Articles, Short Communications, Case Reports and Letter to the Editor.