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Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction
B. Schormair, C. Zhao, S. Bell, M. Didriksen, MS. Nawaz, N. Schandra, A. Stefani, B. Högl, Y. Dauvilliers, CG. Bachmann, D. Kemlink, K. Sonka, W. Paulus, C. Trenkwalder, WH. Oertel, M. Hornyak, M. Teder-Laving, A. Metspalu, GM. Hadjigeorgiou, O....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, metaanalýza
Grantová podpora
U19 AG063911
NIA NIH HHS - United States
390857198
Deutsche Forschungsgemeinschaft (German Research Foundation)
218143125
Deutsche Forschungsgemeinschaft (German Research Foundation)
P50 NS072187
NINDS NIH HHS - United States
310572679
Deutsche Forschungsgemeinschaft (German Research Foundation)
Wellcome Trust - United Kingdom
NLK
ProQuest Central
od 2000-01-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 2000-01-01 do Před 1 rokem
Public Health Database (ProQuest)
od 2000-01-01 do Před 1 rokem
- MeSH
- celogenomová asociační studie * MeSH
- genetická predispozice k nemoci * MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- mendelovská randomizace MeSH
- rizikové faktory MeSH
- strojové učení MeSH
- syndrom neklidných nohou * genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.
1st Faculty of Medicine Charles University Prague Prague Czech Republic
Biomedical Centre Faculty of Medicine in Pilsen Charles University Prague Pilsen Czech Republic
Bragée ME CFS Center Stockholm Sweden
British Heart Foundation Centre of Research Excellence University of Cambridge Cambridge UK
Cancer Research UK Cambridge Institute Li Ka Shing Centre University of Cambridge Cambridge UK
Center for Restless Legs Syndrome Department of Neurology Johns Hopkins University Baltimore MD USA
Department of Clinical Immunology Aalborg University Hospital Aalborg Denmark
Department of Clinical Immunology Aarhus University Hospital Aarhus Denmark
Department of Clinical Immunology Copenhagen University Hospital Rigshospitalet Copenhagen Denmark
Department of Clinical Immunology Odense University Hospital Odense Denmark
Department of Clinical Immunology Zealand University Hospital Køge Denmark
Department of Clinical Medicine Aarhus University Aarhus Denmark
Department of Clinical Medicine University of Copenhagen Copenhagen Denmark
Department of Clinical Neurosciences University of Cambridge Cambridge UK
Department of Haematology and BRC Haematology Theme Churchill Hospital Headington Oxford UK
Department of Haematology University College London Hospitals London UK
Department of Haematology University of Cambridge Cambridge UK
Department of Human Genetics McGill University Montreal Quebec Canada
Department of Medicine Duke University School of Medicine Durham NC USA
Department of Neurology and Neurosurgery McGill University Montreal Quebec Canada
Department of Neurology Emory University Atlanta GA USA
Department of Neurology Ludwig Maximilians University Munich Munich Germany
Department of Neurology Mayo Clinic Jacksonville FL USA
Department of Neurology Methodist Neurological Institute Weill Cornell Medical School Houston TX USA
Department of Neurology Nicosia General Hospital Medical School University of Cyprus Nicosia Cyprus
Department of Neurology Philipps University Marburg Marburg Germany
Department of Neurology University Medical Center Göttingen Göttingen Germany
Department of Neuroscience Mayo Clinic College of Medicine Jacksonville FL USA
Department of Neuroscience University of Copenhagen Copenhagen Denmark
Department of Neurosciences Université de Montréal Montreal Quebec Canada
Department of Neurosurgery University Medical Center Göttingen Göttingen Germany
Department of Oncology University of Cambridge Cambridge UK
Department of Public Health and Welfare National Institute for Health and Welfare Helsinki Finland
Department of Pulmonology Center of Sleep Medicine Charité Universitätsmedizin Berlin Berlin Germany
Duke Clinical Research Institute Duke University School of Medicine Durham NC USA
eCODE Genetics Amgen Reykjavik Iceland
Estonian Genome Center Institute of Genomics University of Tartu Tartu Estonia
German Center for Mental Health partner site Munich Augsburg Munich Augsburg Germany
Health Data Research UK Cambridge Wellcome Genome Campus and University of Cambridge Cambridge UK
Health Data Science Research Centre Fondazione Human Technopole Milan Italy
Institute of Clinical Molecular Biology Kiel University Kiel Germany
Institute of Epidemiology and Social Medicine University of Münster Münster Germany
L'institut du thorax CNRS INSERM Nantes Université Nantes France
Magdalene College Cambridge UK
Munich Cluster for Systems Neurology Munich Germany
Neuropsychiatry Centre Erding München Erding Germany
NHS Blood and Transplant Cambridge Biomedical Campus Cambridge UK
Paracelsus Elena Klinik Kassel Germany
PopGen Biobank and Institute of Epidemiology Christian Albrechts University Kiel Kiel Germany
Radcliffe Department of Medicine and National Health Service Blood and Transplant Oxford UK
Sleep Disorders Clinic Department of Neurology Medical University of Innsbruck Innsbruck Austria
SomnoDiagnostics Osnabrück Germany
Statens Serum Institute Copenhagen Denmark
The Neuro McGill University Montreal Quebec Canada
Victor Phillip Dahdaleh Heart and Lung Research Institute University of Cambridge Cambridge UK
Citace poskytuje Crossref.org
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