Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation
Andlauer TFM, Buck D, Antony G, Bayas A, Bechmann L, Berthele A, Chan A, Gasperi C, Gold R, Graetz C, Haas J, Hecker M, Infante-Duarte C, Knop M, Kuempfel T, Limmroth V, Linker RA, Loleit V, Luessi F, Meuth SG, Muehlau M, Nischwitz S, Paul F, Puetz M, Ruck T, Salmen A, Stangel M, Stellmann JP, Stuerner KH, Tackenberg B, Bergh FT, Tumani H, Warnke C, Weber F, Wiendl H, Wildemann B, Zettl UK, Ziemann U, Zipp F, Arloth J, Weber P, Radivojkov-Blagojevic M, Scheinhardt MO, Dankowski T, Bettecken T, Lichtner P, Czamara D, Carrillo-Roa T, Binder EB, Berger K, Bertram L, Franke A, Gieger C, Herms S, Homuth G, Ising M, Joeckel KH, Kacprowski T, Kloiber S, Laudes M, Lieb W, Lill CM, Lucae S, Meitinger T, Moebus S, Mueller-Nurasyid M, Noethen MM, Petersmann A, Rawal R, Schminke U, Strauch K, Voelzke H, Waldenberger M, Wellmann J, Porcu E, Mulas A, Pitzalis M, Sidore C, Zara I, Cucca F, Zoledziewska M, Ziegler A, Hemmer B, Mueller-Myhsok B (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 2
Pages Range: e1501678
Journal Issue: 6
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.
Involved external institutions
Klinikum Augsburg
Germany (DE)
Max-Planck-Institut für Psychiatrie (Deutsche Forschungsanstalt für Psychiatrie)
Germany (DE)
Westfälische Wilhelms-Universität (WWU) Münster
Germany (DE)
Christian-Albrechts-Universität zu Kiel
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
Universität Greifswald
Germany (DE)
Universität Duisburg-Essen (UDE)
Germany (DE)
Consiglio Nazionale delle Ricerche (CNR) / National Research Council of Italy
Italy (IT)
Universität zu Lübeck
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
Philipps-Universität Marburg
Germany (DE)
Universität Leipzig
Germany (DE)
Ruhr-Universität Bochum (RUB)
Germany (DE)
Johannes Gutenberg-Universität Mainz (JGU)
Germany (DE)
Universitätsklinikum Heidelberg
Germany (DE)
Universität Rostock
Germany (DE)
Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Germany (DE)
Krankenhaus Köln-Merheim - Klinikum der Universität Witten/Herdecke
Germany (DE)
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Germany (DE)
Universitätsklinikum Hamburg-Eppendorf (UKE)
Germany (DE)
Universität Ulm
Germany (DE)
Heinrich-Heine-Universität Düsseldorf
Germany (DE)
Eberhard Karls Universität Tübingen
Germany (DE)
Universitätsmedizin Greifswald / Universitätsklinikum Greifswald
Germany (DE)
Center for Advanced Studies, Research and Development in Sardinia / Centro di Ricerca, Sviluppo e Studi Superiori in Sardegna (CRS4)
Italy (IT)
Germany (DE)
Max-Planck-Institut für Psychiatrie (Deutsche Forschungsanstalt für Psychiatrie)
Germany (DE)
Westfälische Wilhelms-Universität (WWU) Münster
Germany (DE)
Christian-Albrechts-Universität zu Kiel
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
Universität Greifswald
Germany (DE)
Universität Duisburg-Essen (UDE)
Germany (DE)
Consiglio Nazionale delle Ricerche (CNR) / National Research Council of Italy
Italy (IT)
Universität zu Lübeck
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
Philipps-Universität Marburg
Germany (DE)
Universität Leipzig
Germany (DE)
Ruhr-Universität Bochum (RUB)
Germany (DE)
Johannes Gutenberg-Universität Mainz (JGU)
Germany (DE)
Universitätsklinikum Heidelberg
Germany (DE)
Universität Rostock
Germany (DE)
Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Germany (DE)
Krankenhaus Köln-Merheim - Klinikum der Universität Witten/Herdecke
Germany (DE)
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Germany (DE)
Universitätsklinikum Hamburg-Eppendorf (UKE)
Germany (DE)
Universität Ulm
Germany (DE)
Heinrich-Heine-Universität Düsseldorf
Germany (DE)
Eberhard Karls Universität Tübingen
Germany (DE)
Universitätsmedizin Greifswald / Universitätsklinikum Greifswald
Germany (DE)
Center for Advanced Studies, Research and Development in Sardinia / Centro di Ricerca, Sviluppo e Studi Superiori in Sardegna (CRS4)
Italy (IT)
How to cite
APA:
Andlauer, T.F.M., Buck, D., Antony, G., Bayas, A., Bechmann, L., Berthele, A.,... Mueller-Myhsok, B. (2016). Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation. Science Advances, 2(6), e1501678. https://doi.org/10.1126/sciadv.1501678
MLA:
Andlauer, Till F. M., et al. "Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation." Science Advances 2.6 (2016): e1501678.
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