Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

Andlauer, Till F. M.; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Juergen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kuempfel, Tania; Limmroth, Volker; Linker, Ralf A.; Loleit, Verena; Luessi, Felix; Meuth, Sven G.; Muehlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Puetz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stuerner, Klarissa H.; Tackenberg, Bjoern; Bergh, Florian Then; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K.; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O.; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B.; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Joeckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M.; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Mueller-Nurasyid, Martina; Noethen, Markus M.; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Voelzke, Henry; Waldenberger, Melanie; Wellmann, Juergen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

doi:10.1126/sciadv.1501678

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Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

Andlauer, T. F. M., Buck, D., Antony, G., Bayas, A., Bechmann, L., Berthele, A., et al. (2016). Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation. SCIENCE ADVANCES, 2(6): e1501678. doi:10.1126/sciadv.1501678.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002C-6706-D Version Permalink: https://hdl.handle.net/11858/00-001M-0000-002C-6707-B

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Andlauer, Till F. M.¹, Author
Buck, Dorothea², Author
Antony, Gisela², Author
Bayas, Antonios², Author
Bechmann, Lukas², Author
Berthele, Achim², Author
Chan, Andrew², Author
Gasperi, Christiane², Author
Gold, Ralf², Author
Graetz, Christiane², Author
Haas, Juergen², Author
Hecker, Michael², Author
Infante-Duarte, Carmen², Author
Knop, Matthias¹, Author
Kuempfel, Tania², Author
Limmroth, Volker², Author
Linker, Ralf A.², Author
Loleit, Verena², Author
Luessi, Felix², Author
Meuth, Sven G.², Author
Muehlau, Mark², AuthorNischwitz, Sandra¹, Author         Paul, Friedemann², AuthorPuetz, Michael², AuthorRuck, Tobias², AuthorSalmen, Anke², AuthorStangel, Martin², AuthorStellmann, Jan-Patrick², AuthorStuerner, Klarissa H.², AuthorTackenberg, Bjoern², AuthorBergh, Florian Then², AuthorTumani, Hayrettin², AuthorWarnke, Clemens², AuthorWeber, Frank¹, Author         Wiendl, Heinz², AuthorWildemann, Brigitte², AuthorZettl, Uwe K.², AuthorZiemann, Ulf², AuthorZipp, Frauke², AuthorArloth, Janine¹, Author         Weber, Peter¹, Author         Radivojkov-Blagojevic, Milena², AuthorScheinhardt, Markus O.², AuthorDankowski, Theresa², AuthorBettecken, Thomas¹, Author         Lichtner, Peter², AuthorCzamara, Darina¹, Author         Carrillo-Roa, Tania¹, Author         Binder, Elisabeth B.¹, Author         Berger, Klaus², AuthorBertram, Lars², AuthorFranke, Andre², AuthorGieger, Christian², AuthorHerms, Stefan², AuthorHomuth, Georg², AuthorIsing, Marcus¹, Author         Joeckel, Karl-Heinz², AuthorKacprowski, Tim², AuthorKloiber, Stefan¹, Author         Laudes, Matthias², AuthorLieb, Wolfgang², AuthorLill, Christina M.², AuthorLucae, Susanne¹, Author         Meitinger, Thomas², AuthorMoebus, Susanne², AuthorMueller-Nurasyid, Martina², AuthorNoethen, Markus M.², AuthorPetersmann, Astrid², AuthorRawal, Rajesh², AuthorSchminke, Ulf², AuthorStrauch, Konstantin², AuthorVoelzke, Henry², AuthorWaldenberger, Melanie², AuthorWellmann, Juergen², AuthorPorcu, Eleonora², AuthorMulas, Antonella², AuthorPitzalis, Maristella², AuthorSidore, Carlo², AuthorZara, Ilenia², AuthorCucca, Francesco², AuthorZoledziewska, Magdalena², AuthorZiegler, Andreas², AuthorHemmer, Bernhard², AuthorMüller-Myhsok, Bertram¹, Author          more..

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1Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137
2external, ou_persistent22

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Free keywords: Multiple sclerosis, genome-wide association study, DNA methylation, L3MBTL3, MAZ, ERG, DLEU1, SHMT1

Abstract: We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.

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Language(s): eng - English

Dates: Published Online: 2016-06

Publication Status: Published online

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Identifiers: ISI: 000380073800009
DOI: 10.1126/sciadv.1501678

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Title: SCIENCE ADVANCES

Source Genre: Journal

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Pages: - Volume / Issue: 2 (6) Sequence Number: e1501678 Start / End Page: - Identifier: ISSN: 2375-2548