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

Autor: Laabs BH; Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany., Lohmann K; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany., Vollstedt EJ; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany., Reinberger T; Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany., Nuxoll LM; Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany., Kilic-Berkmen G; Department of Neurology, Emory University, Atlanta, Georgia, USA., Perlmutter JS; Department of Neurology, Radiology and Neuroscience, Washington University School of Medicine, St. Louis, Missouri, USA., Loens S; Institute of Systems Motor Science, CBBM, University of Lübeck, Lübeck, Germany., Cruchaga C; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA., Franke A; Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany., Dobricic V; Lübeck Interdisciplinary Platform for Genome Analysis, University of Lübeck, Lübeck, Germany., Hinrichs F; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany., Grözinger A; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany., Altenmüller E; Institute of Music Physiology and Musician's Medicine, Hanover University of Music, Drama and Media, Hanover, Germany., Bellows S; Parkinson's Disease Center and Movement Disorder Clinic, Baylor College of Medicine, Houston, Texas, USA., Boesch S; Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria., Bressman SB; Department of Neurology, Mount Sinai Beth Israel Medical Center, New York, New York, USA.; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Duque KR; 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., Espay AJ; 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., Ferbert A; Department of Neurology, Kassel School of Medicine, Klinikum Kassel, Kassel, Germany., Feuerstein JS; Department of Neurology, School of Medicine, University of Colorado, Aurora, Colorado, USA., Frank S; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA., Gasser T; Department of Neurology, University of Tübingen, Tübingen, Germany.; Hertie Institute for Clinical Brain Research and DZNE, University of Tübingen, Tübingen, Germany., Haslinger B; Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany., Jech R; Department of Neurology, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic., Kaiser F; Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.; Essener Zentrum für Seltene Erkrankungen, University Hospital Essen, Essen, Germany., Kamm C; Department of Neurology, University Medical Centre Rostock, Rostock, Germany., Kollewe K; Clinic for Neurology, Hannover Medical School, Hannover, Germany., Kühn AA; Department of Neurology and Experimental Neurology, Charité-University Medicine, Berlin, Germany., LeDoux MS; Veracity Neuroscience LLC, Memphis, Tennessee, USA.; Department of Psychology, University of Memphis, Memphis, Tennessee, USA., Lohmann E; Department of Neurology, University of Tübingen, Tübingen, Germany.; Hertie Institute for Clinical Brain Research and DZNE, University of Tübingen, Tübingen, Germany., Mahajan A; Department of Neurological Sciences, RUSH University, Chicago, Illinois, USA., Münchau A; Institute of Systems Motor Science, CBBM, University of Lübeck, Lübeck, Germany., Multhaupt-Buell T; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Pantelyat A; Department of Neurology, Johns Hopkins Medicine, Baltimore, Maryland, USA., Pirio Richardson SE; Department of Neurology, University of New Mexico, Albuquerque, New Mexico, USA., Raymond D; Department of Neurology, Mount Sinai Beth Israel Medical Center, New York, New York, USA., Reich SG; University of Maryland School of Medicine, Baltimore, Maryland, USA., Saunders Pullman R; Department of Neurology, Mount Sinai Beth Israel Medical Center, New York, New York, USA.; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Schormair B; Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.; Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany., Sharma N; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Sichani AH; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts, USA., Simonyan K; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Neurological Sciences, RUSH University, Chicago, Illinois, USA.; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts, USA., Volkmann J; Department of Neurology, University Hospital Würzburg, Würzburg, Germany., Wagle Shukla A; Department of Neurology, University of Florida, Gainesville, Florida, USA., Winkelmann J; Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.; Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany.; Munich Cluster for Systems Neurology, SyNergy, Munich, Germany., Wright LJ; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA., Zech M; Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.; Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany., Zeuner KE; Clinic for Neurology, Christian-Albrechts-University, Kiel, Germany., Zittel S; Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Kasten M; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.; Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany., Sun YV; Department of Epidemiology, Emory University Rollins School of Public Health, Emory University, Atlanta, Georgia, USA., Bäumer T; Institute of Systems Motor Science, CBBM, University of Lübeck, Lübeck, Germany., Brüggemann N; Department of Neurology, University of Lübeck, Lübeck, Germany., Ozelius LJ; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Jinnah HA; Department of Neurology, Emory University, Atlanta, Georgia, USA., Klein C; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany., König IR; Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany.
Jazyk: angličtina
Zdroj: Movement disorders : official journal of the Movement Disorder Society [Mov Disord] 2024 Nov; Vol. 39 (11), pp. 2110-2116. Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1002/mds.29968
Abstrakt: 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.
(© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
Databáze: MEDLINE