{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:01:25Z","timestamp":1789912885381,"version":"4.0.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":240,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Study Objectives<\/jats:title>\n                    <jats:p>Restless legs syndrome (RLS) is predominantly idiopathic (iRLS), with a prevalence of 2%\u201310% in Europe. In end-stage renal disease patients (ESRD), uremic RLS (uRLS) is substantially more prevalent, with estimates of 24%\u201328%. Its pathophysiology has not been fully uncovered. Therefore, we investigated potential genetic and phenotypic risk factors for uRLS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We performed case\u2013control genome-wide association studies (GWAS) on ESRD patients with and without RLS from two German and one Greek ESRD study populations (cases\/controls: 186\/356, 80\/176, 134\/357). We applied a polygenic risk score (PRS) for iRLS to four groups: uRLS cases, uremic controls, a group of iRLS cases and European 1000G individuals. Additionally, we investigated RLS associations with phenotype data available in one German dataset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No SNP reached genome-wide significance in any single dataset or meta-analyses. The mean iRLS PRS was significantly higher in uRLS cases compared to uremic controls (p\u00a0=\u20099.47e-10) and European 1000G individuals (p\u00a0=\u20099.93e-6) and significantly smaller compared to iRLS cases (p\u00a0=\u20094.84e-5). Among 164 available lead SNPs at known RLS risk loci, rs113851554 at the MEIS1 locus, the strongest known iRLS-associated variant, was significant after Bonferroni correction (0.05\/164\u2009=\u20093.05e-4) in the German uremic meta-analysis (p\u00a0=\u20095.73e-5). Two loci rs36127502 and rs5769388, previously not associated with RLS, show suggestive significance (p\u00a0=\u20091.37e-7, p\u00a0=\u20091.92e-7) in a meta-analysis combining the three GWAS datasets. Regular smoking and parathormone levels were nominally associated with RLS in ESRD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings indicate that uRLS and iRLS share a substantial part of their genetic architecture, while also pointing to candidate signals specific to uRLS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/sleepadvances\/zpag095","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T17:40:33Z","timestamp":1788025233000},"source":"Crossref","is-referenced-by-count":0,"title":["Genome-wide association study of restless legs syndrome in end-stage renal disease"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6089-6043","authenticated-orcid":false,"given":"Noah","family":"Risse","sequence":"first","affiliation":[{"name":"Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Institute of Neurogenomics , Neuherberg ,","place":["Germany"]},{"name":"Institute of Human Genetics, TUM School of Medicine and Health, Technical University of Munich , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Harrer","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Institute of Neurogenomics , Neuherberg ,","place":["Germany"]},{"name":"Institute of Human Genetics, TUM School of Medicine and Health, Technical University of Munich , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgos K","family":"Sakkas","sequence":"additional","affiliation":[{"name":"Department of Physical Education and Sport Science, University of Thessaly , Trikala, Thessaly 42100 ,","place":["Greece"]},{"name":"Department of Life Sciences, School of Life and Health Sciences, University of Nicosia , Nicosia, 2417 ,","place":["Cyprus"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Stefanidis","sequence":"additional","affiliation":[{"name":"Department of Nephrology, School of Medicine, University of Thessaly , Larisa ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Schandra","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Institute of Neurogenomics , Neuherberg ,","place":["Germany"]},{"name":"Institute of Human Genetics, TUM School of Medicine and Health, Technical University of Munich , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4259-8824","authenticated-orcid":false,"given":"Ambra","family":"Stefani","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Innsbruck , Innsbruck ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Wildt","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Innsbruck , Innsbruck ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Dauvilliers","sequence":"additional","affiliation":[{"name":"Sleep\u2013Wake Disorders Centre, Department of Neurology, Gui de Chauliac Hospital , Montpellier ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios M","family":"Hadjigeorgiou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nicosia General Hospital Medical School, University of Cyprus , Nicosia ,","place":["Cyprus"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Institute of Neurogenomics , Neuherberg ,","place":["Germany"]},{"name":"Institute of Human Genetics, TUM School of Medicine and Health, Technical University of Munich , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Winkelmann","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Institute of Neurogenomics , Neuherberg ,","place":["Germany"]},{"name":"Institute of Human Genetics, TUM School of Medicine and Health, Technical University of Munich , Munich ,","place":["Germany"]},{"name":"Munich Cluster for Systems Neurology (SyNergy) , Munich ,","place":["Germany"]},{"name":"German Center for Mental Health (DZPG), partner site Munich\u2013Augsburg , Munich\u2013Augsburg 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