Genome-wide association study finds no replicable common risk loci in isolated dystonia, suggesting that whole-genome sequencing is needed to uncover underlying genetic drivers.
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.
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Laabs et al. (2024) studied this question.
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