Language

English

Publication Date

11-1-2024

Journal

Movement Disorders

DOI

10.1002/mds.29968

PMID

39287592

PMCID

PMC11975433

PubMedCentral® Posted Date

11-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Background: Despite considerable heritability, previous smaller genome-wide association studies (GWASs) have not identified any robust genetic risk factors for isolated dystonia.

Objective: The objective of this study was to perform a large-scale GWAS in a well-characterized, multicenter sample of >6000 individuals to identify genetic risk factors for isolated dystonia.

Methods: Array-based GWASs were performed on autosomes for 4303 dystonia participants and 2362 healthy control subjects of European ancestry with subgroup analysis based on age at onset, affected body regions, and a newly developed clinical score. Another 736 individuals were used for validation.

Results: This GWAS identified no common genome-wide significant loci that could be replicated despite sufficient power to detect meaningful effects. Power analyses imply that the effects of individual variants are likely very small.

Conclusions: Moderate single-nucleotide polymorphism-based heritability indicates that common variants do not contribute to isolated dystonia in this cohort. Sequence-based GWASs (eg, by whole-genome sequencing) might help to better understand the genetic basis. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords

Humans, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Male, Female, Risk Factors, Genetic Predisposition to Disease, Dystonia, Adult, Middle Aged, Dystonic Disorders, isolated dystonia, GWAS, age at onset, clinical score, case–control

Published Open-Access

yes

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