{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T14:39:01Z","timestamp":1777646341447,"version":"3.51.4"},"reference-count":59,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DA 1657\/2-1"],"award-info":[{"award-number":["DA 1657\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Emmy Noether Research Group"],"award-info":[{"award-number":["Emmy Noether Research Group"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Genet Epigenet"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>ALS is a fatal motor neuron disease that displays a broad variety of phenotypes ranging from early fatal courses to slowly progressing and rather benign courses. Such divergence can also be seen in genetic ALS cases with varying phenotypes bearing specific mutations, suggesting epigenetic mechanisms like DNA methylation act as disease modifiers. However, the epigenotype dictated by, in addition to other mechanisms, DNA methylation is also strongly influenced by the individual\u2019s genotype. Hence, we performed a DNA methylation study using EPIC arrays on 7 monozygotic (MZ) twin pairs discordant for ALS in whole blood, which serves as an ideal model for eliminating the effects of the genetic-epigenetic interplay to a large extent. We found one CpG site showing intra-pair hypermethylation in the affected co-twins, which maps to the Glutamate Ionotropic Receptor Kainate Type Subunit 1 gene ( GRIK1). Additionally, we found 4 DMPs which were subsequently confirmed using 2 different statistical approaches. Differentially methylated regions or blocks could not be detected within the scope of this work. In conclusion, we revealed that despite a low sample size, monozygotic twin studies discordant for the disease can bring new insights into epigenetic processes in ALS, pointing to new target loci for further investigations.<\/jats:p>","DOI":"10.1177\/25168657231172159","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T06:44:38Z","timestamp":1683182678000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["DNA Methylation Analysis in Monozygotic Twins Discordant for ALS in Blood Cells"],"prefix":"10.1177","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3861-0181","authenticated-orcid":false,"given":"Volkan","family":"Yazar","sequence":"first","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), German Center for Neurodegenerative Diseases, Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8105-6123","authenticated-orcid":false,"given":"Wolfgang P","family":"Ruf","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ulm University, Ulm, Baden-W\u00fcrttemberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antje","family":"Knehr","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ulm University, Ulm, Baden-W\u00fcrttemberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kornelia","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ulm University, Ulm, Baden-W\u00fcrttemberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole","family":"Ammerpohl","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Ulm University & Ulm University Medical Center, Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin M","family":"Danzer","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), German Center for Neurodegenerative Diseases, Ulm, Germany"},{"name":"Department of Neurology, Ulm University, Ulm, Baden-W\u00fcrttemberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert C","family":"Ludolph","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), German Center for Neurodegenerative Diseases, Ulm, Germany"},{"name":"Department of Neurology, Ulm University, Ulm, Baden-W\u00fcrttemberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2023,5,4]]},"reference":[{"key":"bibr1-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2022.04.003"},{"key":"bibr2-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj0264"},{"key":"bibr3-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-020-0118-3"},{"key":"bibr4-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-1062"},{"key":"bibr5-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.107151"},{"key":"bibr6-25168657231172159","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2015.1049183"},{"key":"bibr7-25168657231172159","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.8839.2"},{"key":"bibr8-25168657231172159","unstructured":"R: The R Project for Statistical Computing. Accessed July 14, 2022. https:\/\/www.r-project.org\/"},{"key":"bibr9-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu049"},{"key":"bibr10-25168657231172159","doi-asserted-by":"publisher","DOI":"10.2217\/epi.12.21"},{"key":"bibr11-25168657231172159","doi-asserted-by":"publisher","DOI":"10.4161\/epi.23470"},{"key":"bibr12-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"bibr13-25168657231172159","unstructured":"R: Econometric tools for performance and risk analysis. Accessed July 14, 2022. http:\/\/braverock.com\/brian\/R\/PerformanceAnalytics\/html\/PerformanceAnalytics-package.html"},{"key":"bibr14-25168657231172159","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.706907."},{"key":"bibr15-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0213-x"},{"key":"bibr16-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-86"},{"key":"bibr17-25168657231172159","unstructured":"Ggplot2\n                      . Accessed July 14, 2022. https:\/\/link.springer.com\/book\/10.1007\/978-3-319-24277-4"},{"key":"bibr18-25168657231172159","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v067.i01"},{"key":"bibr19-25168657231172159","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v082.i13"},{"key":"bibr20-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"bibr21-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv907"},{"key":"bibr22-25168657231172159","doi-asserted-by":"publisher","DOI":"10.21105\/joss.03139"},{"key":"bibr23-25168657231172159","unstructured":"Zeileis A, Hothorn T. Diagnostic Checking in Regression Relationships. Published online 2015. Accessed July 16, 2022. https:\/\/www.semanticscholar.org\/paper\/Diagnostic-Checking-in-Regression-Relationships-Zeileis-Hothorn\/58b4d02ee546c30e31a3ead4ccb956fc451e6e95"},{"key":"bibr24-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1101\/gr.229102"},{"key":"bibr25-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131."},{"key":"bibr26-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-128"},{"key":"bibr27-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8935-8-6"},{"key":"bibr28-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-021-00746-5"},{"key":"bibr29-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx513"},{"key":"bibr30-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-2-r30"},{"key":"bibr31-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-10-r115"},{"key":"bibr32-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-019-2804-7"},{"key":"bibr33-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77"},{"key":"bibr34-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44765-4"},{"key":"bibr35-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008175"},{"key":"bibr36-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn233"},{"key":"bibr37-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00835.x"},{"key":"bibr38-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-021-01083-9"},{"key":"bibr39-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-019-5761-7"},{"key":"bibr40-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1111\/2041-210X.13434"},{"key":"bibr41-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101700"},{"key":"bibr42-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2011.10.001"},{"key":"bibr43-25168657231172159","doi-asserted-by":"publisher","DOI":"10.3390\/cells9020381"},{"key":"bibr44-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1177\/1073858417705059"},{"key":"bibr45-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2009.05.004"},{"key":"bibr46-25168657231172159","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.2.642"},{"key":"bibr47-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9781107337459"},{"key":"bibr48-25168657231172159","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.678350."},{"key":"bibr49-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8335"},{"key":"bibr50-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1080\/10543406.2020.1730878"},{"key":"bibr51-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1101\/gr.176933.114"},{"issue":"2","key":"bibr52-25168657231172159","first-page":"1","volume":"13","author":"Yazar V","year":"2023","journal-title":"J Parkinson\u2019s Dis"},{"key":"bibr53-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2444"},{"key":"bibr54-25168657231172159","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00231."},{"key":"bibr55-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1002\/bies.202100127"},{"key":"bibr56-25168657231172159","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22158042"},{"key":"bibr57-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02446-6"},{"key":"bibr58-25168657231172159","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abh2169"},{"key":"bibr59-25168657231172159","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11060754"}],"container-title":["Epigenetics Insights"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/25168657231172159","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/25168657231172159","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/25168657231172159","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:34:58Z","timestamp":1777444498000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/25168657231172159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":59,"alternative-id":["10.1177\/25168657231172159"],"URL":"https:\/\/doi.org\/10.1177\/25168657231172159","relation":{},"ISSN":["2516-8657","2516-8657"],"issn-type":[{"value":"2516-8657","type":"print"},{"value":"2516-8657","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1]]},"article-number":"25168657231172159"}}