{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T04:10:35Z","timestamp":1759205435801,"version":"3.41.2"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100008522","name":"University of Illinois at Chicago","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008522","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000125","name":"National Institute for Occupational Safety and Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000125","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007015","name":"University of Wisconsin-Madison","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007015","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Study Objectives<\/jats:title><jats:p>Patients with unexplained hypersomnolence have significant impairment related to daytime sleepiness and excessive sleep duration, the biological bases of which are poorly understood. This investigation sought to examine relationships between objectively measured hypersomnolence phenotypes and epigenetic modification of candidate hypersomnolence genes to advance this line of inquiry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty-eight unmedicated clinical patients with unexplained hypersomnolence were evaluated using overnight ad libitum polysomnography, multiple sleep latency testing, infrared pupillometry, and the psychomotor vigilance task. DNA methylation levels on CpG sites annotated to 11 a priori hypersomnolence candidate genes were assessed for statistical association with hypersomnolence measures using independent regression models with adjusted local index of significance (aLIS) P-value threshold of 0.05.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nine CpG sites exhibited significant associations between DNA methylation levels and total sleep time measured using ad libitum polysomnography (aLIS p-value &amp;lt; .05). All nine differentially methylated CpG sites were annotated to the paired box 8 (PAX8) gene and its related antisense gene (PAX8-AS1). Among these nine differentially methylated positions was a cluster of five CpG sites located in the body of the PAX8 gene and promoter of PAX8-AS1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrates that PAX8\/PAX8-AS1 DNA methylation levels are associated with total sleep time in persons with unexplained hypersomnolence. Given prior investigations that have implicated single nucleotide polymorphisms in PAX8\/PAX8-AS1 with habitual sleep duration, further research that clarifies the role of DNA methylation levels on these genes in the phenotypic expression of total sleep time is warranted.<\/jats:p><\/jats:sec>","DOI":"10.1093\/sleep\/zsab108","type":"journal-article","created":{"date-parts":[[2021,6,19]],"date-time":"2021-06-19T01:08:30Z","timestamp":1624064910000},"source":"Crossref","is-referenced-by-count":5,"title":["PAX8\/PAX8-AS1 DNA methylation levels are associated with objective sleep duration in persons with unexplained hypersomnolence using a deep phenotyping approach"],"prefix":"10.1093","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2619-5654","authenticated-orcid":false,"given":"David T","family":"Plante","sequence":"first","affiliation":[{"name":"Department of Psychiatry , Madison, WI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ligia A","family":"Papale","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery , Madison, WI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andy","family":"Madrid","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery , Madison, WI"},{"name":"Neuroscience Training Program, University of Wisconsin \u2013 Madison , Madison, WI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse D","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Psychology , Madison, WI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael L","family":"Prairie","sequence":"additional","affiliation":[{"name":"University of Minnesota School of Medicine , Minneapolis, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0637-4137","authenticated-orcid":false,"given":"Reid S","family":"Alisch","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery , Madison, WI"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"issue":"9560","key":"2023032819410169200_","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S0140-6736(07)60237-2","article-title":"Narcolepsy with cataplexy","volume":"369","author":"Dauvilliers","year":"2007","journal-title":"Lancet."},{"issue":"7","key":"2023032819410169200_","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1164\/ajrccm.163.7.2103055e","article-title":"Is the measurement of sleepiness the Holy Grail of sleep medicine?","volume":"163","author":"Bliwise","year":"2001","journal-title":"Am J Respir Crit Care Med."},{"key":"2023032819410169200_","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/978-88-470-5388-5_30","article-title":"Sleepiness Assessment.","volume-title":"Sleepiness and Human Impact Assessment.","author":"Pizza","year":"2014"},{"issue":"12","key":"2023032819410169200_","doi-asserted-by":"crossref","DOI":"10.1093\/sleep\/zsx164","article-title":"Test-retest reliability of the multiple sleep latency test in central disorders of hypersomnolence","volume":"40","author":"Lopez","year":"2017","journal-title":"Sleep."},{"issue":"1","key":"2023032819410169200_","doi-asserted-by":"crossref","first-page":"65","DOI":"10.5664\/jcsm.6882","article-title":"The MSLT is repeatable in narcolepsy type 1 but not narcolepsy type 2: a retrospective patient study","volume":"14","author":"Ruoff","year":"2018","journal-title":"J Clin Sleep Med."},{"issue":"8","key":"2023032819410169200_","doi-asserted-by":"crossref","first-page":"789","DOI":"10.5664\/jcsm.2922","article-title":"Test-retest reliability of the multiple sleep latency test in narcolepsy without cataplexy and idiopathic hypersomnia","volume":"9","author":"Trotti","year":"2013","journal-title":"J Clin Sleep Med."},{"issue":"4","key":"2023032819410169200_","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1378\/chest.101.4.898","article-title":"Maintenance of wakefulness test and multiple sleep latency test. 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