{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T14:35:39Z","timestamp":1777905339161,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T00:00:00Z","timestamp":1632614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R100-2011-9332"],"award-info":[{"award-number":["R100-2011-9332"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Tic spectrum disorder (TSD) is an umbrella term which includes Gilles de la Tourette syndrome (GTS) and chronic tic disorder (CTD). They are considered highly heritable, yet the genetic components remain largely unknown. In this study we aimed to investigate disease-associated DNA methylation differences to identify genes and pathways which may be implicated in TSD aetiology. For this purpose, we performed an exploratory analysis of the genome-wide DNA methylation patterns in whole blood samples of 16 monozygotic twin pairs, of which eight were discordant and six concordant for TSD, while two pairs were asymptomatic. Although no sites reached genome-wide significance, we identified several sites and regions with a suggestive significance, which were located within or in the vicinity of genes with biological functions associated with neuropsychiatric disorders. The two top genes identified (TSC1 and CRYZ\/TYW3) and the enriched pathways and components (phosphoinosides and PTEN pathways, and insulin receptor substrate binding) are related to, or have been associated with, the PI3K\/AKT\/mTOR pathway. Genes in this pathway have previously been associated with GTS, and mTOR signalling has been implicated in a range of neuropsychiatric disorders. It is thus possible that altered mTOR signalling plays a role in the complex pathogenesis of TSD.<\/jats:p>","DOI":"10.3390\/genes12101510","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T04:55:33Z","timestamp":1632718533000},"page":"1510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["EWAS of Monozygotic Twins Implicate a Role of mTOR Pathway in Pathogenesis of Tic Spectrum Disorder"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2016-3670","authenticated-orcid":false,"given":"Mathis","family":"Hildonen","sequence":"first","affiliation":[{"name":"Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7863-4300","authenticated-orcid":false,"given":"Amanda M.","family":"Levy","sequence":"additional","affiliation":[{"name":"Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine S\u00f8holm","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department for Congenital Disorders, Statens Serum Institut, 2300 Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas","family":"Bybjerg-Grauholm","sequence":"additional","affiliation":[{"name":"Department for Congenital Disorders, Statens Serum Institut, 2300 Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Skytthe","sequence":"additional","affiliation":[{"name":"Epidemiology and Biostatistics, Department of Public Health, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0279-1865","authenticated-orcid":false,"given":"Nanette M.","family":"Debes","sequence":"additional","affiliation":[{"name":"Tourette Clinics, Department of Paediatrics, Copenhagen University Hospital, 2730 Herlev, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qihua","family":"Tan","sequence":"additional","affiliation":[{"name":"Epidemiology and Biostatistics, Department of Public Health, University of Southern Denmark, 5000 Odense, Denmark"},{"name":"Unit of Human Genetics, Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4777-5802","authenticated-orcid":false,"given":"Zeynep","family":"T\u00fcmer","sequence":"additional","affiliation":[{"name":"Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1007\/s00787-018-01272-7","article-title":"Tic disorders revisited: Introduction of the term \u201ctic spectrum disorders\u201d","volume":"28","author":"Sambrani","year":"2019","journal-title":"Eur. 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