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团队科学方法在全球范围内揭示单基因帕金森病。

Team Science Approaches to Unravel Monogenic Parkinson's Disease on a Global Scale.

机构信息

Institute of Neurogenetics, University of Luebeck, Luebeck, Germany.

Department of Neurology, University Clinic Schleswig-Holstein, Luebeck, Germany.

出版信息

Mov Disord. 2024 Oct;39(10):1868-1873. doi: 10.1002/mds.29925. Epub 2024 Jul 30.

Abstract

BACKGROUND

Until recently, about three-quarters of all monogenic Parkinson's disease (PD) studies were performed in European/White ancestry, thereby severely limiting our insights into genotype-phenotype relationships at a global scale.

OBJECTIVE

To identify the multi-ancestry spectrum of monogenic PD.

METHODS

The first systematic approach to embrace monogenic PD worldwide, The Michael J. Fox Foundation Global Monogenic PD Project, contacted authors of publications reporting individuals carrying pathogenic variants in known PD-causing genes. In contrast, the Global Parkinson's Genetics Program's Monogenic Network took a different approach by targeting PD centers underrepresented or not yet represented in the medical literature.

RESULTS

In this article, we describe combining both efforts in a merger project resulting in a global monogenic PD cohort with the buildup of a sustainable infrastructure to identify the multi-ancestry spectrum of monogenic PD and enable studies of factors modifying penetrance and expressivity of monogenic PD.

CONCLUSIONS

This effort demonstrates the value of future research based on team science approaches to generate comprehensive and globally relevant results. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

摘要

背景

直到最近,大约四分之三的单基因帕金森病(PD)研究都是在欧洲/白种人血统中进行的,这极大地限制了我们在全球范围内对基因型-表型关系的了解。

目的

确定单基因 PD 的多种血统谱。

方法

第一个系统的方法来拥抱单基因 PD 全世界,迈克尔 J. 福克斯基金会全球单基因 PD 项目,联系报告携带已知 PD 致病基因变异的个体的出版物的作者。相比之下,全球帕金森氏症遗传学计划的单基因网络采取了不同的方法,针对在医学文献中代表性不足或尚未有代表性的 PD 中心。

结果

在本文中,我们描述了将这两种努力结合在一个合并项目中,结果是一个具有可持续基础设施的全球单基因 PD 队列,用于确定单基因 PD 的多种血统谱,并能够研究修饰单基因 PD 外显率和表现度的因素。

结论

这项工作表明,基于团队科学方法的未来研究具有价值,可以产生全面和全球相关的结果。

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