ITSN1功能丧失变体赋予帕金森病高风险。

Loss-of-function variants in ITSN1 confer high risk of Parkinson's disease.

作者信息

Skuladottir Astros Th, Tragante Vinicius, Sveinbjornsson Gardar, Helgason Hannes, Sturluson Arni, Bjornsdottir Anna, Jonsson Palmi, Palmadottir Vala, Sveinsson Olafur A, Jensson Brynjar O, Gudjonsson Sigurjon A, Ivarsdottir Erna V, Gisladottir Rosa S, Gunnarsson Arni F, Walters G Bragi, Jonsdottir Gudrun A, Thorgeirsson Thorgeir E, Bjornsdottir Gyda, Holm Hilma, Gudbjartsson Daniel F, Sulem Patrick, Stefansson Hreinn, Stefansson Kari

机构信息

deCODE genetics/Amgen Inc., Reykjavik, Iceland.

Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

出版信息

NPJ Parkinsons Dis. 2024 Aug 15;10(1):140. doi: 10.1038/s41531-024-00752-9.

DOI:10.1038/s41531-024-00752-9

PMID:39147844

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11327306/

Abstract

Parkinson's disease (PD) is a debilitating neurodegenerative disorder and its rising global incidence highlights the need for the identification of modifiable risk factors. In a gene-based burden test of rare variants (8647 PD cases and 777,693 controls) we discovered a novel association between loss-of-function variants in ITSN1 and PD. This association was further supported with burden data from the Neurodegenerative Disease Knowledge Portal and the Accelerating Medicines Partnership Parkinson's Disease Knowledge Platform. Our findings show that Rho GTPases and disruptions in synaptic vesicle transport may be involved in the pathogenesis of PD, pointing to the possibility of novel therapeutic approaches.

摘要

帕金森病（PD）是一种使人衰弱的神经退行性疾病，其在全球范围内发病率不断上升，凸显了识别可改变风险因素的必要性。在一项基于基因的罕见变异负担测试中（8647例帕金森病患者和777,693名对照），我们发现ITSN1功能丧失变异与帕金森病之间存在新的关联。神经退行性疾病知识门户和加速药物合作帕金森病知识平台的负担数据进一步支持了这一关联。我们的研究结果表明，Rho GTP酶和突触小泡运输中断可能参与帕金森病的发病机制，这为新的治疗方法提供了可能性。