| Title: | Rare-Variant Burden Analysis of Dystonia Genes in Parkinson's Disease |
| Journal: | Movement Disorders |
| Published: | 1 Aug 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42541459/ |
| DOI: | https://doi.org/10.1002/mds.70463 |
Publication 21101
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Abstract
BACKGROUND: Dystonia frequently coexists with Parkinson's disease (PD), yet the extent of genetic overlap remains insufficiently explored.</p>
OBJECTIVE: The aim was to examine whether rare variants in dystonia-related genes are associated with PD or early-onset PD (EOPD).</p>
METHODS: We curated 44 dystonia-related genes using the Online Mendelian Inheritance in Man (OMIM) and the Movement Disorder Society report on hereditary dystonia. Whole-genome sequencing data from 5315 PD patients, including 300 EOPD patients, and 36,902 controls across the Accelerating Medicines Partnership-Parkinson's Disease (AMP-PD) and UK Biobank European cohorts were analyzed. Rare-variant burden analysis was performed using the optimized sequence kernel association test (SKAT-O) and MetaSKAT.</p>
RESULTS: In the analyses of all PD patients, no association survived multiple-testing correction. Conversely, exploratory EOPD analyses identified five significant genes (ATP5MC3, DNAJC12, KMT2B, TBC1D24, TMEM151A); however, these signals were driven by small numbers of variants and were not robust to leave-one-variant-out analyses.</p>
CONCLUSIONS: Rare variants in dystonia-related genes are not major contributors to overall PD risk. Signals observed in the EOPD subset require replication in larger cohorts. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>
5 Authors
- Sajanth Kanagasingam
- Sitki Cem Parlar
- Lang Liu
- Ziv Gan-Or
- Konstantin Senkevich
1 Application
| Application ID | Title |
|---|---|
| 45551 | Mechanistic modelling of neurodevelopment, neuroplasticity, and neurodegeneration |
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