SynthesisNature genetics2024
Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.
Abstract readMeta-Analysis
In one paragraph
Synthesis in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Multi ancestry genome wide association meta analysis of urinary aMT6s levels.Scientific reports · 2026Pooled it
- Association between restless legs syndrome and erectile dysfunction: a systematic review and meta-analysis.Sleep and biological rhythms · 2026Review
- Phenotype Refinement Influences GWAS-Implicated Variant Effect Sizes for Insomnia.Journal of sleep research · 2026Article
- Changes in sleep characteristics in Parkinson's disease: a prospective 5-year follow-up study.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2026Article
- Emerging genetics of sleep and circadian disorders.Current opinion in pediatrics · 2026Article
- Serum Concentrations of Cytokines in Patients With Restless Legs Syndrome.Journal of sleep research · 2026Article
- Comparative Peripheral Blood Transcriptomic Profiles in Parkinson's Disease and Restless Legs Syndrome: An Exploratory Between-Cohort Analysis.International journal of molecular sciences · 2026Article
- Cerebrospinal Fluid from Restless Legs Syndrome Patients Reduces Iron Uptake in Blood-Brain Barrier Endothelial Cells by Disrupting the Regulation of Transferrin Receptors.Annals of neurology · 2026Article
- Polygenic risk scores in neurological disorders: restless legs syndrome as a translational model.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Integration of Brain Proteomes and Genome-Wide Association Data Identifies GLO1 as a Candidate Causal Gene and Therapeutic Target for Restless Legs Syndrome.International journal of molecular sciences · 2026Article
- Ancestry-specific and multi-ancestry genome-wide association studies of restless legs syndrome.medRxiv : the preprint server for health sciences · 2026Article
- Restless Legs Syndrome: A Network Model of Iron-Dependent Neuromodulation-A Narrative Review.Brain sciences · 2026Review
- Treatment of restless legs syndrome by acupuncture combined with medicine based on pathophysiological mechanism.Frontiers in medicine · 2026Review
- The evolving treatment landscape of restless legs syndrome.Therapeutic advances in neurological disorders · 2026Review
- Genome-wide association study of restless legs syndrome in end-stage renal disease.Sleep advances : a journal of the Sleep Research Society · 2026Article
- Central and peripheral excitability in restless limbs syndrome.Brain communications · 2026Article
- Shared genetic architecture between Parkinson's disease and self-reported sleep-related traits implicates theSleep advances : a journal of the Sleep Research Society · 2026Article
- Sleep Related Movement Disorders: What's New and Changing Clinical Practice.Journal of sleep research · 2025Review
- The Interplay Between Sleep and Mental Health: A Genetic Perspective.Biological psychiatry · 2025Review
- From Normal Variation in Sleep to Clinical Sleep Disorders: Genetic Insights from Over One Million Individuals.medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
69 authors.
Barbara Schormair *Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. barbara.schormair@helmholtz-munich.de.ORCID http://orcid.org/0000-0003-0942-5243
Chen Zhao *Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Steven Bell *Department of Oncology, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-6774-3149
Maria DidriksenDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-4856-496X
Muhammad S NawazdeCODE Genetics/Amgen, Reykjavik, Iceland.
Nathalie SchandraInstitute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Ambra StefaniSleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.ORCID http://orcid.org/0000-0003-4259-8824
Birgit HöglSleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Yves DauvilliersSleep-Wake Disorders Center, Department of Neurology, Hôpital Gui-de-Chauliac, CHU Montpellier, Institut des Neurosciences de Montpellier, INSERM, Université de Montpellier, Montpellier, France.
Cornelius G BachmannSomnoDiagnostics, Osnabrück, Germany.
David KemlinkDepartment of Neurology and Centre of Clinical Neuroscience, Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
Karel SonkaDepartment of Neurology and Centre of Clinical Neuroscience, Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
Walter PaulusDepartment of Neurology, Ludwig Maximilians University Munich, Munich, Germany.
Claudia TrenkwalderParacelsus-Elena-Klinik, Kassel, Germany.
Wolfgang H OertelInstitute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Magdolna HornyakNeuropsychiatry Centre Erding/München, Erding, Germany.
Maris Teder-LavingEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Andres MetspaluEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Georgios M HadjigeorgiouDepartment of Neurology, Nicosia General Hospital Medical School, University of Cyprus, Nicosia, Cyprus.ORCID http://orcid.org/0000-0001-5386-4273
Olli PoloBragée ME/CFS Center, Stockholm, Sweden.
Ingo FietzeDepartment of Pulmonology, Center of Sleep Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Owen A RossDepartment of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0003-4813-756X
Zbigniew K WszolekDepartment of Neurology, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0001-5487-1053
Abubaker IbrahimSleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Melanie BergmannSleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Volker KittkeInstitute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0001-8866-1388
Philip HarrerInstitute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Joseph DowsettDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-5381-2633
Sofiene CheniniSleep-Wake Disorders Center, Department of Neurology, Hôpital Gui-de-Chauliac, CHU Montpellier, Institut des Neurosciences de Montpellier, INSERM, Université de Montpellier, Montpellier, France.
Sisse Rye OstrowskiDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-5288-3851
Erik SørensenDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Christian ErikstrupDepartment of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-6551-6647
Ole B PedersenDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-2312-5976
Mie Topholm BruunDepartment of Clinical Immunology, Odense University Hospital, Odense, Denmark.ORCID http://orcid.org/0000-0002-8819-5388
Kaspar R NielsenDepartment of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
Adam S ButterworthBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-6915-9015
Nicole SoranzoNational Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-1095-3852
Willem H OuwehandDepartment of Haematology, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-7744-1790
David J RobertsNational Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK.
John DaneshBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Brendan BurchellMagdalene College, Cambridge, UK.
Nicholas A Furlotte23andMe, Inc., Sunnyvale, CA, USA.
Priyanka Nandakumar23andMe, Inc., Sunnyvale, CA, USA.
23andMe Research Team
D.E.S.I.R. study group
Christopher J EarleyCenter for Restless Legs Syndrome, Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
William G OndoDepartment of Neurology, Methodist Neurological Institute, Weill Cornell Medical School, Houston, TX, USA.
Lan XiongThe Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada.
Alex DesautelsCentre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada.
Markus PerolaClinical and Molecular Metabolism Research Program (CAMM), Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Pavel VodickaDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic.
Christian DinaL'institut du thorax, CNRS, INSERM, Nantes Université, Nantes, France.ORCID http://orcid.org/0000-0002-7722-7348
Monika StollDepartment of Genetic Epidemiology, Institute for Human Genetics, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0002-2711-4281
Andre FrankeInstitute of Clinical Molecular Biology, Kiel University, Kiel, Germany.ORCID http://orcid.org/0000-0003-1530-5811
Wolfgang LiebPopGen Biobank and Institute of Epidemiology, Christian Albrechts University Kiel, Kiel, Germany.ORCID http://orcid.org/0000-0003-2544-4460
Alexandre F R StewartJohn and Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.ORCID http://orcid.org/0000-0003-2673-9164
Svati H ShahDepartment of Medicine, Duke University School of Medicine, Durham, NC, USA.
Christian GiegerInstitute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0001-6986-9554
Annette PetersInstitute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0001-6645-0985
David B RyeDepartment of Neurology, Emory University, Atlanta, GA, USA.
Guy A RouleauThe Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada.
Klaus BergerInstitute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
Hreinn StefanssondeCODE Genetics/Amgen, Reykjavik, Iceland.
Henrik UllumStatens Serum Institute, Copenhagen, Denmark.
Kari StefanssondeCODE Genetics/Amgen, Reykjavik, Iceland.
David A Hinds23andMe, Inc., Sunnyvale, CA, USA.ORCID http://orcid.org/0000-0002-4911-803X
Emanuele Di AngelantonioBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Konrad OexleInstitute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0001-7447-2252
Juliane WinkelmannInstitute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0002-3074-599X
Funding
Technology and Remote Assessment CoreU19AG063911 · NIA · MAYO CLINIC ROCHESTER · PI Bradley F Boeve · 2019 to 2026
$120.9MNeuropathology CoreP50NS072187 · NINDS · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 2010 to 2017
$8.7MDeutsche Forschungsgemeinschaft (German Research Foundation) 218143125Deutsche Forschungsgemeinschaft (German Research Foundation) 310572679Deutsche Forschungsgemeinschaft (German Research Foundation) 390857198Medical Research Council MR/L003120/1NIA NIH HHS U19 AG063911NINDS NIH HHS P50 NS072187Wellcome Trust
Abstract
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 (r
Indexed as
Genetic Predisposition to DiseaseGenome-Wide Association StudyRestless Legs SyndromeFemaleHumansMachine LearningMaleMendelian Randomization AnalysisPolymorphism, Single NucleotideRisk Factors
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.