Genetic Risk Factors in Isolated Dystonia Escape Genome-Wide Association Studies

Mov Disord. 2024 Nov;39(11):2110-2116. doi: 10.1002/mds.29968. Epub 2024 Sep 17.

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: GWAS; age at onset; case–control; clinical score; isolated dystonia.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Dystonia* / genetics
  • Dystonic Disorders / genetics
  • Female
  • Genetic Predisposition to Disease* / genetics
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide* / genetics
  • Risk Factors