{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T03:42:25Z","timestamp":1788320545464,"version":"build-2803163510"},"reference-count":75,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:00:00Z","timestamp":1654560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG027810"],"award-info":[{"award-number":["U01 AG027810"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG042124"],"award-info":[{"award-number":["U01 AG042124"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG042139"],"award-info":[{"award-number":["U01 AG042139"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG042140"],"award-info":[{"award-number":["U01 AG042140"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG042143"],"award-info":[{"award-number":["U01 AG042143"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG042145"],"award-info":[{"award-number":["U01 AG042145"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG042168"],"award-info":[{"award-number":["U01 AG042168"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AR066160"],"award-info":[{"award-number":["U01 AR066160"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1 TR000128"],"award-info":[{"award-number":["UL1 TR000128"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR051124"],"award-info":[{"award-number":["R01 AR051124"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RC2 AR058973"],"award-info":[{"award-number":["RC2 AR058973"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL071194"],"award-info":[{"award-number":["R01 HL071194"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL070848"],"award-info":[{"award-number":["R01 HL070848"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL070847"],"award-info":[{"award-number":["R01 HL070847"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL070842"],"award-info":[{"award-number":["R01 HL070842"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL070841"],"award-info":[{"award-number":["R01 HL070841"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL070837"],"award-info":[{"award-number":["R01 HL070837"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL070838"],"award-info":[{"award-number":["R01 HL070838"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HHSN268201500003I"],"award-info":[{"award-number":["HHSN268201500003I"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95159"],"award-info":[{"award-number":["N01-HC-95159"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95160"],"award-info":[{"award-number":["N01-HC-95160"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95161"],"award-info":[{"award-number":["N01-HC-95161"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95162"],"award-info":[{"award-number":["N01-HC-95162"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95163"],"award-info":[{"award-number":["N01-HC-95163"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95164"],"award-info":[{"award-number":["N01-HC-95164"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95165"],"award-info":[{"award-number":["N01-HC-95165"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95166"],"award-info":[{"award-number":["N01-HC-95166"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95167"],"award-info":[{"award-number":["N01-HC-95167"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95168"],"award-info":[{"award-number":["N01-HC-95168"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95169"],"award-info":[{"award-number":["N01-HC-95169"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["UL1-TR-000040"],"award-info":[{"award-number":["UL1-TR-000040"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["UL1-TR-001079"],"award-info":[{"award-number":["UL1-TR-001079"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["UL1-TR-001881"],"award-info":[{"award-number":["UL1-TR-001881"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["DK06349"],"award-info":[{"award-number":["DK06349"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01-HL-135818"],"award-info":[{"award-number":["R01-HL-135818"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","award":["3200B0-105993"],"award-info":[{"award-number":["3200B0-105993"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","award":["3200B0-118308"],"award-info":[{"award-number":["3200B0-118308"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","award":["33CSCO-122661"],"award-info":[{"award-number":["33CSCO-122661"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","award":["33CS30-139468"],"award-info":[{"award-number":["33CS30-139468"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","award":["33CS30-148401"],"award-info":[{"award-number":["33CS30-148401"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Study Objectives<\/jats:title><jats:p>Periodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e., discovery, replication, and joint meta-analysis) of four cohorts (MrOS, the Wisconsin Sleep Cohort Study, HypnoLaus, and MESA), comprised of 6843 total subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The MrOS study and Wisconsin Sleep Cohort Study (N\u2005=\u20051745 cases) were used for discovery. Replication in the HypnoLaus and MESA cohorts (1002 cases) preceded joint meta-analysis. We also performed LD score regression, estimated heritability, and computed genetic correlations between potentially associated traits such as restless leg syndrome (RLS) and insomnia. The causality and direction of the relationships between PLMS and RLS was evaluated using Mendelian randomization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found 2 independent loci were significantly associated with PLMS: rs113851554 (p\u2005=\u20053.51\u2005\u00d7\u200510\u221212, \u03b2\u2005=\u20050.486), an SNP located in a putative regulatory element of intron eight of MEIS1 (2p14); and rs9369062 (p\u2005=\u20053.06\u2005\u00d7\u200510\u221222, \u03b2\u2005=\u20050.2093), a SNP located in the intron region of BTBD9 (6p12); both of which were also lead signals in RLS GWAS. PLMS is genetically correlated with insomnia, risk of stroke, and RLS, but not with iron deficiency. Pleiotropy adjusted Mendelian randomization analysis identified a causal effect of RLS on PLMS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Because PLMS is more common than RLS, PLMS may have multiple causes and additional studies are needed to further validate these findings.<\/jats:p><\/jats:sec>","DOI":"10.1093\/sleep\/zsac121","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T13:12:03Z","timestamp":1654607523000},"source":"Crossref","is-referenced-by-count":23,"title":["The genetic etiology of periodic limb movement in sleep"],"prefix":"10.1093","volume":"46","author":[{"given":"Jacob L","family":"Edelson","sequence":"first","affiliation":[{"name":"Department of Biomedical Data Sciences, Stanford University School of Medicine , Palo Alto, CA 94603 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan D","family":"Schneider","sequence":"additional","affiliation":[{"name":"Stanford\/VA Alzheimer\u2019s Research Center , Palo Alto, CA 94603 , USA"},{"name":"Stanford Department of Psychiatry and Behavioral Medicine, Center for Sleep Sciences and Medicine, Stanford University School of Medicine , Palo Alto, CA 94603 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Amar","sequence":"additional","affiliation":[{"name":"Stanford Department of Cardiovascular Medicine, Stanford University School of Medicine , Palo Alto, CA 94603 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Brink-Kjaer","sequence":"additional","affiliation":[{"name":"Stanford Department of Psychiatry and Behavioral Medicine, Center for Sleep Sciences and Medicine, Stanford University School of Medicine , Palo Alto, CA 94603 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5693-9293","authenticated-orcid":false,"given":"Katie L","family":"Cederberg","sequence":"additional","affiliation":[{"name":"Stanford Department of Psychiatry and Behavioral Medicine, Center for Sleep Sciences and Medicine, Stanford University School of Medicine , Palo Alto, CA 94603 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Kutalik","sequence":"additional","affiliation":[{"name":"University Center for Primary Care and Public Health, University of Lausanne , Lausanne 1010 , Switzerland"},{"name":"Swiss Institute of Bioinformatics , Lausanne 1015 , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika W","family":"Hagen","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison, School of Medicine and Public Health, Department of Population Health Sciences , Madison, WI 53726 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E","family":"Peppard","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison, School of Medicine and Public Health, Department of Population Health Sciences , Madison, WI 53726 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila Farias","family":"Tempaku","sequence":"additional","affiliation":[{"name":"Department of Psychobiology, Universidade Federal de S\u00e3o Paulo , S\u00e3o Paulo 04021002 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Tufik","sequence":"additional","affiliation":[{"name":"Department of Psychobiology, Universidade Federal de S\u00e3o Paulo , S\u00e3o Paulo 04021002 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S","family":"Evans","sequence":"additional","affiliation":[{"name":"California Pacific Medical Center, Research Institute , San Francisco, CA 94107 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Stone","sequence":"additional","affiliation":[{"name":"California Pacific Medical Center, Research Institute , San Francisco, CA 94107 , USA"},{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco , CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Tranah","sequence":"additional","affiliation":[{"name":"California Pacific Medical Center, Research Institute , San Francisco, CA 94107 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-0673","authenticated-orcid":false,"given":"Brian","family":"Cade","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women\u2019s Hospital , Boston, MA 102115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Redline","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women\u2019s Hospital , Boston, MA 102115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Haba-Rubio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne , Lausanne 1011 , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Heinzer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne , Lausanne 1011 , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4548-8500","authenticated-orcid":false,"given":"Pedro","family":"Marques-Vidal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne , Lausanne 1011 , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0765-896X","authenticated-orcid":false,"given":"Peter","family":"Vollenweider","sequence":"additional","affiliation":[{"name":"Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne , Lausanne 1011 , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Winkelmann","sequence":"additional","affiliation":[{"name":"Institute of Neurogenomics, Helmholtz Center Munich (HMGU) Technical University of Munich , 81675 Munich , Germany"},{"name":"School of Medicine, Institute of Human Genetics Synergy, Cluster of Neuroscience Munich , 52246 Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences, Stanford University School of Medicine , Palo Alto, CA 94603 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Mignot","sequence":"additional","affiliation":[{"name":"Stanford Department of Psychiatry and Behavioral Medicine, Center for Sleep Sciences and Medicine, Stanford University School of Medicine , Palo Alto, CA 94603 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,7]]},"reference":[{"key":"2023041207233463000_","volume-title":"The AASM Manual for the Scoring of Sleep and Associated Events: Rules","author":"Iber","year":"2007"},{"issue":"11","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1016\/j.clinph.2018.08.022","article-title":"Periodic limb movements in sleep: prevalence and associated sleepiness in the Wisconsin Sleep Cohort","volume":"129","author":"Leary","year":"2018","journal-title":"Clin Neurophysiol."},{"issue":"5","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/NRL.0b013e3181422589","article-title":"Restless legs syndrome and periodic limb movements during sleep: diagnosis and treatment","volume":"13","author":"Karatas","year":"2007","journal-title":"Neurologist"},{"key":"2023041207233463000_","article-title":"Periodic limb movement disorder.","volume-title":"StatPearls","author":"Joseph","year":"2021"},{"issue":"9","key":"2023041207233463000_","first-page":"1221","article-title":"Periodic limb movements during sleep: population prevalence, clinical correlates, and racial differences","volume":"31","author":"Scofield","year":"2008","journal-title":"Sleep"},{"issue":"1","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/S0022-3999(02)00443-9","article-title":"Prevalence of restless legs syndrome and periodic limb movement disorder in the general population","volume":"53","author":"Ohayon","year":"2002","journal-title":"J Psychosom Res."},{"issue":"4","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"945","DOI":"10.5665\/sleep.5660","article-title":"Sleep characteristics in early stages of chronic kidney disease in the HypnoLaus Cohort","volume":"39","author":"Ogna","year":"2016","journal-title":"Sleep"},{"issue":"6","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.biopsych.2005.04.022","article-title":"Antidepressants and periodic leg movements of sleep","volume":"58","author":"Yang","year":"2005","journal-title":"Biol Psychiatry."},{"key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"101274","DOI":"10.1016\/j.smrv.2020.101274","article-title":"Iron deficiency and sleep - a scoping review","volume":"51","author":"Leung","year":"2020","journal-title":"Sleep Med Rev."},{"issue":"11","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.sleep.2015.05.015","article-title":"Association of low ferritin with PLM in the Wisconsin sleep cohort","volume":"16","author":"Li","year":"2015","journal-title":"Sleep Med"},{"issue":"1","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1007\/s13311-021-01019-4","article-title":"Restless legs syndrome: contemporary diagnosis and treatment","volume":"18","author":"Gossard","year":"2021","journal-title":"Neurotherapeutics"},{"issue":"4, Sleep Neurology","key":"2023041207233463000_","first-page":"1005","article-title":"Restless legs syndrome and sleep-related movement disorders","volume":"23","author":"Trotti","year":"2017","journal-title":"Continuum Minneapolis, MN"},{"issue":"3","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/0891-5849(90)90072-Q","article-title":"Protective effects of superoxide dismutase on acute reperfusion injury of gerbil brain","volume":"8","author":"Uyama","year":"1990","journal-title":"Free Radic Biology Med"},{"issue":"3","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.amjmed.2012.06.039","article-title":"Vascular risk factors, cardiovascular disease, and restless legs syndrome in men","volume":"126","author":"Winter","year":"2013","journal-title":"Am J M"},{"issue":"3","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1002\/ana.24593","article-title":"Prevalence and determinants of periodic limb movements in the general population","volume":"79","author":"Haba-Rubio","year":"2016","journal-title":"Ann Neurol"},{"issue":"14","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1161\/CIRCULATIONAHA.112.112698","article-title":"Prospective study of restless legs syndrome and coronary heart disease among women","volume":"126","author":"Li","year":"2012","journal-title":"Circulation"},{"issue":"7","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.5665\/sleep.4800","article-title":"Risk of cardiovascular disease associated with a restless legs syndrome diagnosis in a retrospective cohort study from Kaiser Permanente Northern California","volume":"38","author":"Van Den Eeden","year":"2015","journal-title":"Sleep"},{"issue":"11","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.jagp.2016.04.003","article-title":"Restless legs syndrome and depression: effect mediation by disturbed sleep and periodic limb movements","volume":"24","author":"Koo","year":"2016","journal-title":"Am J Geriatr Psychiatry."},{"issue":"1","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"368","DOI":"10.3390\/ijerph17010368","article-title":"Why are women prone to restless legs syndrome?","volume":"17","author":"Seeman","year":"2020","journal-title":"Int J Environ Res Public Health."},{"issue":"8","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s11910-019-0965-4","article-title":"Update on restless legs syndrome: from mechanisms to treatment","volume":"19","author":"Gonzalez-Latapi","year":"2019","journal-title":"Curr Neurol Neurosci Rep"},{"issue":"11","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/S1474-4422(17)30327-7","article-title":"Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis","volume":"16","author":"Schormair","year":"2017","journal-title":"Lancet Neurol."},{"issue":"1","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s42003-020-01430-1","article-title":"Large genome-wide association study identifies three novel risk variants for restless legs syndrome","volume":"3","author":"Didriksen","year":"2020","journal-title":"Commun Biol."},{"issue":"3","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/s41588-018-0333-3","article-title":"Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways","volume":"51","author":"Jansen","year":"2019","journal-title":"Nat Genet."},{"issue":"11","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/sleep\/zsy164","article-title":"Reassessing GWAS findings for the shared genetic basis of insomnia and restless legs syndrome","volume":"41","author":"El Gewely","year":"2018","journal-title":"Sleep"},{"issue":"9","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.5665\/sleep.4006","article-title":"Periodic leg movements during sleep are associated with polymorphisms in BTBD9, TOX3\/BC034767, MEIS1, MAP2K5\/SKOR1, and PTPRD","volume":"37","author":"Moore","year":"2014","journal-title":"Sleep"},{"issue":"12","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1111\/j.1532-5415.2011.03731.x","article-title":"Associations between sleep architecture and sleep-disordered breathing and cognition in older community-dwelling men: The Osteoporotic Fractures in Men Sleep Study","volume":"59","author":"Blackwell","year":"2011","journal-title":"J Am Geriatr Soc."},{"key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1471-2261-8-6","article-title":"The CoLaus study: a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome","volume":"8","author":"Firmann","year":"2008","journal-title":"BMC Cardiovasc Disord."},{"issue":"6","key":"2023041207233463000_","first-page":"877","article-title":"Racial\/ethnic differences in sleep disturbances: the multi-ethnic study of atherosclerosis (MESA)","volume":"38","author":"Chen","year":"2015","journal-title":"Sleep"},{"issue":"5","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1378\/chest.14-0970","article-title":"International classification of sleep disorders-third edition: highlights and modifications","volume":"146","author":"Sateia","year":"2014","journal-title":"Chest"},{"issue":"17","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1056\/NEJM199304293281704","article-title":"The occurrence of sleep-disordered breathing among middle-aged adults","volume":"328","author":"Young","year":"1993","journal-title":"N Engl J Med."},{"issue":"12","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"e114565","DOI":"10.1371\/journal.pone.0114565","article-title":"Design and validation of a periodic leg movement detector [published correction appears in PLoS One. 2015;10(9):e0138205]","volume":"9","author":"Moore","year":"2014","journal-title":"PLoS One."},{"issue":"5","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.cct.2005.05.005","article-title":"Overview of recruitment for the osteoporotic fractures in men study (MrOS)","volume":"26","author":"Blank","year":"2005","journal-title":"Contemp Clin Trials."},{"issue":"11","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/j.sleep.2015.07.017","article-title":"Genetic associations of periodic limb movements of sleep in the elderly for the MrOS sleep study","volume":"16","author":"Winkelman","year":"2015","journal-title":"Sleep Med."},{"issue":"4","key":"2023041207233463000_","first-page":"709","article-title":"Event scoring in polysomnography: scoring arousals, respiratory events, and leg movements","volume":"11","author":"Bibbs","year":"2005","journal-title":"Respir Care Clin N Am"},{"issue":"8","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"zsy106","DOI":"10.1093\/sleep\/zsy106","article-title":"Restless legs syndrome and periodic limb movements during sleep in the Multi-Ethnic Study of Atherosclerosis","volume":"41","author":"Doan","year":"2018","journal-title":"Sleep"},{"key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.sleep.2017.09.014","article-title":"Clinical significance of periodic limb movements during sleep: the HypnoLaus study","volume":"41","author":"Haba-Rubio","year":"2018","journal-title":"Sleep Med."},{"issue":"4","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/S2213-2600(15)00043-0","article-title":"Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study","volume":"3","author":"Heinzer","year":"2015","journal-title":"Lancet Respir Med"},{"issue":"8","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.sleep.2014.03.025","article-title":"Restless legs syndrome\/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance","volume":"15","author":"Allen","year":"2014","journal-title":"Sleep Med."},{"issue":"2","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.sleep.2006.01.001","article-title":"The official World Association of Sleep Medicine (WASM) standards for recording and scoring periodic leg movements in sleep (PLMS) and wakefulness (PLMW) developed in collaboration with a task force from the International Restless Legs Syndrome Study Group (IRLSSG)","volume":"7","author":"Zucconi","year":"2006","journal-title":"Sleep Med."},{"issue":"3","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.gheart.2016.08.004","article-title":"Legacy of MESA","volume":"11","author":"Olson","year":"2016","journal-title":"Glob Heart"},{"issue":"6","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"e1000529","DOI":"10.1371\/journal.pgen.1000529","article-title":"A flexible and accurate genotype imputation method for the next generation of genome-wide association studies","volume":"5","author":"Howie","year":"2009","journal-title":"PLoS Genet."},{"issue":"7319","key":"2023041207233463000_","first-page":"1061","article-title":"A map of human genome variation from population-scale sequencing [published correction appears in Nature. 2011 May 26;473(7348):544. Xue, Yali [added]; Cartwright, Reed A [added]; Altshuler, David L [corrected to Altshuler, David]; Kebbel, Andrew [corrected to Keebler, Jonathan]; Koko-Gonzales, Paula [corrected to Kokko-Gonzales, Paula]; Nickerson, Debbie A [corrected to Nickerson, Debo]","volume":"467","author":"1000 Genomes Project Consortium.","year":"2010","journal-title":"Nature"},{"issue":"7","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1038\/ng2088","article-title":"A new multipoint method for genome-wide association studies by imputation of genotypes","volume":"39","author":"Marchini","year":"2007","journal-title":"Nat Genet."},{"issue":"3","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet."},{"issue":"4","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/gepi.20303","article-title":"Estimation of the multiple testing burden for genomewide association studies of nearly all common variants","volume":"32","author":"Pe\u2019er","year":"2008","journal-title":"Genet Epidemiol."},{"issue":"2","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/ng1706","article-title":"Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies","volume":"38","author":"Skol","year":"2006","journal-title":"Nat Genet"},{"issue":"17","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","article-title":"METAL: fast and efficient meta-analysis of genome wide association scans","volume":"26","author":"Willer","year":"2010","journal-title":"Bioinformatics"},{"issue":"7414","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ"},{"issue":"11","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/ng.3406","article-title":"An atlas of genetic correlations across human diseases and traits","volume":"47","author":"Bulik-Sullivan","year":"2015","journal-title":"Nat Genet."},{"issue":"7","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet Epidemiol."},{"issue":"R2","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"R195","DOI":"10.1093\/hmg\/ddy163","article-title":"Evaluating the potential role of pleiotropy in Mendelian randomization studies","volume":"27","author":"Hemani","year":"2018","journal-title":"Hum Mol Genet"},{"issue":"7","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/s41588-020-0631-4","article-title":"Mendelian randomization accounting for correlated and uncorrelated pleiotropic effects using genome-wide summary statistics [published correction appears in Nat Genet. 2020 May 29;]","volume":"52","author":"Morrison","year":"2020","journal-title":"Nat Genet."},{"issue":"3","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1093\/ije\/dyq151","article-title":"Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants","volume":"40","author":"Pierce","year":"2011","journal-title":"Int J Epidemiol."},{"issue":"6","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1093\/ije\/dyx034","article-title":"MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data","volume":"46","author":"Yavorska","year":"2017","journal-title":"Int J Epidemiol."},{"issue":"11","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"zsz165","DOI":"10.1093\/sleep\/zsz165","article-title":"Individual periodic limb movements with arousal are temporally associated with nonsustained ventricular tachycardia: a case-crossover analysis","volume":"42","author":"May","year":"2019","journal-title":"Sleep"},{"issue":"1","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S1389-9457(99)00007-6","article-title":"Clinical and polysomnographic features in DQB1*0602 positive and negative narcolepsy patients: results from the modafinil clinical trial","volume":"1","author":"Hong","year":"2000","journal-title":"Sleep Med."},{"issue":"12","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1093\/sleep\/29.12.1587","article-title":"Different periodicity and time structure of leg movements during sleep in narcolepsy\/cataplexy and restless legs syndrome","volume":"29","author":"Ferri","year":"2006","journal-title":"Sleep"},{"issue":"3","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1365-2869.2007.00601.x","article-title":"Periodic leg movements during sleep and wakefulness in narcolepsy","volume":"16","author":"Dauvilliers","year":"2007","journal-title":"J Sleep Res."},{"issue":"12","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/j.sleep.2013.07.019","article-title":"Sertraline and periodic limb movements during sleep: an 8-week open-label study in depressed patients with insomnia","volume":"14","author":"Zhang","year":"2013","journal-title":"Sleep Med."},{"issue":"9","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.5664\/jcsm.7338","article-title":"Respiratory-related leg movements of sleep are associated with serotonergic antidepressants but not bupropion","volume":"14","author":"McCall","year":"2018","journal-title":"J Clin Sleep Med."},{"issue":"5","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"661","DOI":"10.5665\/sleep.2622","article-title":"Mirtazapine provokes periodic leg movements during sleep in young healthy men","volume":"36","author":"Fulda","year":"2013","journal-title":"Sleep"},{"issue":"6","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S1388-2457(02)00066-4","article-title":"Time-dependent variation in cerebral and autonomic activity during periodic leg movements in sleep: implications for arousal mechanisms","volume":"113","author":"Sforza","year":"2002","journal-title":"Clin Neurophysiol."},{"issue":"3","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1046\/j.1365-2869.2000.00202.x","article-title":"EEG arousals and awakenings in relation with periodic leg movements during sleep","volume":"9","author":"Karadeniz","year":"2000","journal-title":"J Sleep Res."},{"issue":"1","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.sleep.2012.09.021","article-title":"Experimentally induced arousals do not elicit periodic leg motor activity during sleep in normal subjects","volume":"14","author":"Ferri","year":"2013","journal-title":"Sleep Med."},{"issue":"10","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1016\/j.clinph.2004.04.024","article-title":"Influence of sleep stage and wakefulness on spectral EEG activity and heart rate variations around periodic leg movements","volume":"115","author":"Lavoie","year":"2004","journal-title":"Clin Neurophysiol."},{"issue":"3-4","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1159\/000487666","article-title":"Sleep-related leg movements in patients with transient ischemic attack and controls","volume":"79","author":"Schipper","year":"2018","journal-title":"Eur Neurol."},{"issue":"2","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1161\/STROKEAHA.120.029847","article-title":"Dynamic prevalence of sleep disorders following stroke or transient ischemic attack: systematic review and meta-analysis","volume":"52","author":"Hasan","year":"2021","journal-title":"Stroke"},{"issue":"4","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"zsx023","DOI":"10.1093\/sleep\/zsx023","article-title":"Associations of incident cardiovascular events with restless legs syndrome and periodic leg movements of sleep in older men, for the Outcomes of Sleep Disorders in Older Men Study (MrOS Sleep Study)","volume":"40","author":"Winkelman","year":"2017","journal-title":"Sleep"},{"issue":"2","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"e1001599","DOI":"10.1371\/journal.pmed.1001599","article-title":"Obstructive sleep apnea and risk of cardiovascular events and all-cause mortality: a decade-long historical cohort study","volume":"11","author":"Kendzerska","year":"2014","journal-title":"PLoS Med."},{"key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.sleep.2016.08.009","article-title":"Longitudinal relationships of periodic limb movements during sleep and incident atrial fibrillation","volume":"25","author":"May","year":"2016","journal-title":"Sleep Med."},{"issue":"2","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3390\/jdb4020014","article-title":"Hox genes in cardiovascular development and diseases","volume":"4","author":"Roux","year":"2016","journal-title":"J Dev Biol"},{"issue":"4","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1093\/ije\/dyx254","article-title":"Mendelian randomization with Egger pleiotropy correction and weakly informative Bayesian priors","volume":"47","author":"Schmidt","year":"2018","journal-title":"Int J Epidemiol."},{"key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","article-title":"Interpreting findings from Mendelian randomization using the MR-Egger method","volume":"32","author":"Burgess","year":"2017","journal-title":"Eur J Epidemiol."},{"key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/s41467-020-20516-2","article-title":"A. Rivas. Graphical analysis for phenome-wide causal discovery in genotyped population-scale biobanks","volume":"12","author":"Amar","year":"2021","journal-title":"Nat Commun."},{"issue":"3","key":"2023041207233463000_","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/sleep\/19.3.196","article-title":"Persistence of repetitive EEG arousals (K-alpha complexes) in RLS patients treated with L-DOPA","volume":"19","author":"Montplaisir","year":"1996","journal-title":"Sleep"}],"container-title":["Sleep"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/sleep\/advance-article-pdf\/doi\/10.1093\/sleep\/zsac121\/48180176\/zsac121.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/sleep\/article-pdf\/46\/4\/zsac121\/49799332\/zsac121.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/sleep\/article-pdf\/46\/4\/zsac121\/49799332\/zsac121.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T19:44:55Z","timestamp":1700682295000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/sleep\/article\/doi\/10.1093\/sleep\/zsac121\/6603639"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,7]]},"references-count":75,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,6,7]]},"published-print":{"date-parts":[[2023,4,12]]}},"URL":"https:\/\/doi.org\/10.1093\/sleep\/zsac121","relation":{},"ISSN":["0161-8105","1550-9109"],"issn-type":[{"value":"0161-8105","type":"print"},{"value":"1550-9109","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,4,1]]},"published":{"date-parts":[[2022,6,7]]},"article-number":"zsac121"}}