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.

Clinic for Neurology Christian Albrechts University Kiel Germany

Clinic for Neurology Hannover Medical School Hannover Germany

Department of Epidemiology Emory University Rollins School of Public Health Emory University Atlanta Georgia USA

Department of Neurological Sciences RUSH University Chicago Illinois USA

Department of Neurology and Experimental Neurology Charité University Medicine Berlin Germany

Department of Neurology Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA

Department of Neurology Charles University Prague 1st Faculty of Medicine and General University Hospital Prague Prague Czech Republic

Department of Neurology Emory University Atlanta Georgia USA

Department of Neurology Icahn School of Medicine at Mount Sinai New York New York USA

Department of Neurology Johns Hopkins Medicine Baltimore Maryland USA

Department of Neurology Kassel School of Medicine Klinikum Kassel Kassel Germany

Department of Neurology Klinikum rechts der Isar Technical University of Munich School of Medicine Munich Germany

Department of Neurology Massachusetts General Hospital and Harvard Medical School Boston Massachusetts USA

Department of Neurology Medical University of Innsbruck Innsbruck Austria

Department of Neurology Mount Sinai Beth Israel Medical Center New York New York USA

Department of Neurology Radiology and Neuroscience Washington University School of Medicine St Louis Missouri USA

Department of Neurology School of Medicine University of Colorado Aurora Colorado USA

Department of Neurology University Hospital Würzburg Würzburg Germany

Department of Neurology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Neurology University Medical Centre Rostock Rostock Germany

Department of Neurology University of Florida Gainesville Florida USA

Department of Neurology University of Lübeck Lübeck Germany

Department of Neurology University of New Mexico Albuquerque New Mexico USA

Department of Neurology University of Tübingen Tübingen Germany

Department of Neurology Washington University School of Medicine St Louis Missouri USA

Department of Otolaryngology Head and Neck Surgery Massachusetts Eye and Ear and Harvard Medical School Boston Massachusetts USA

Department of Psychiatry and Psychotherapy University of Lübeck Lübeck Germany

Department of Psychiatry Washington University School of Medicine St Louis Missouri USA

Department of Psychology University of Memphis Memphis Tennessee USA

Essener Zentrum für Seltene Erkrankungen University Hospital Essen Essen Germany

Hertie Institute for Clinical Brain Research and DZNE University of Tübingen Tübingen Germany

Institute for Cardiogenetics University of Lübeck Lübeck Germany

Institute of Clinical Molecular Biology Kiel University Kiel Germany

Institute of Human Genetics School of Medicine Technical University of Munich Munich Germany

Institute of Human Genetics University Hospital Essen University Duisburg Essen Essen Germany

Institute of Medical Biometry and Statistics University of Lübeck Lübeck Germany

Institute of Music Physiology and Musician's Medicine Hanover University of Music Drama and Media Hanover Germany

Institute of Neurogenetics University of Lübeck Lübeck Germany

Institute of Neurogenomics Helmholtz Zentrum München Munich Germany

Institute of Systems Motor Science CBBM University of Lübeck Lübeck Germany

James J and Joan A Gardner Family Center for Parkinson's Disease and Movement Disorders Neurology and Rehabilitation Medicine College of Medicine University of Cincinnati Cincinnati Ohio USA

Lübeck Interdisciplinary Platform for Genome Analysis University of Lübeck Lübeck Germany

Munich Cluster for Systems Neurology SyNergy Munich Germany

Parkinson's Disease Center and Movement Disorder Clinic Baylor College of Medicine Houston Texas USA

University of Maryland School of Medicine Baltimore Maryland USA

Veracity Neuroscience LLC Memphis Tennessee USA

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