Genome-wide determinants of mortality and motor progression in Parkinson's disease.

Journal

NPJ Parkinson's disease

ISSN: 2373-8057

Titre abrégé: NPJ Parkinsons Dis

Pays: United States

ID NLM: 101675390

Informations de publication

Date de publication:
07 Jun 2024

Historique:

received: 05 02 2024

accepted: 24 05 2024

medline: 8 6 2024

pubmed: 8 6 2024

entrez: 7 6 2024

Statut: epublish

Résumé

There are 90 independent genome-wide significant genetic risk variants for Parkinson's disease (PD) but currently only five nominated loci for PD progression. The biology of PD progression is likely to be of central importance in defining mechanisms that can be used to develop new treatments. We studied 6766 PD patients, over 15,340 visits with a mean follow-up of between 4.2 and 15.7 years and carried out genome-wide survival studies for time to a motor progression endpoint, defined by reaching Hoehn and Yahr stage 3 or greater, and death (mortality). There was a robust effect of the APOE ε4 allele on mortality in PD. We also identified a locus within the TBXAS1 gene encoding thromboxane A synthase 1 associated with mortality in PD. We also report 4 independent loci associated with motor progression in or near MORN1, ASNS, PDE5A, and XPO1. Only the non-Gaucher disease causing GBA1 PD risk variant E326K, of the known PD risk variants, was associated with mortality in PD. Further work is needed to understand the links between these genomic variants and the underlying disease biology. However, these may represent new candidates for disease modification in PD.

Identifiants

DOI: 10.1038/s41531-024-00729-8 PMID: 38849413

pubmed: 38849413

doi: 10.1038/s41531-024-00729-8

pii: 10.1038/s41531-024-00729-8

doi:

Types de publication

Journal Article

Langues

eng

Pagination

113

Subventions

Organisme : Parkinson's UK

ID : H-1703

Pays : United Kingdom

Organisme : RCUK | Medical Research Council (MRC)

ID : MR/R007446/1

Informations de copyright

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