Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation
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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, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A; Loleit, Verena; Luessi, Felix; Meuth, Sven G; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H; Tackenberg, Björn; Then Bergh, Florian; 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; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram.
in: SCI ADV, Jahrgang 2, Nr. 6, 06.2016, S. e1501678.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation
AU - Andlauer, Till F M
AU - Buck, Dorothea
AU - Antony, Gisela
AU - Bayas, Antonios
AU - Bechmann, Lukas
AU - Berthele, Achim
AU - Chan, Andrew
AU - Gasperi, Christiane
AU - Gold, Ralf
AU - Graetz, Christiane
AU - Haas, Jürgen
AU - Hecker, Michael
AU - Infante-Duarte, Carmen
AU - Knop, Matthias
AU - Kümpfel, Tania
AU - Limmroth, Volker
AU - Linker, Ralf A
AU - Loleit, Verena
AU - Luessi, Felix
AU - Meuth, Sven G
AU - Mühlau, Mark
AU - Nischwitz, Sandra
AU - Paul, Friedemann
AU - Pütz, Michael
AU - Ruck, Tobias
AU - Salmen, Anke
AU - Stangel, Martin
AU - Stellmann, Jan-Patrick
AU - Stürner, Klarissa H
AU - Tackenberg, Björn
AU - Then Bergh, Florian
AU - Tumani, Hayrettin
AU - Warnke, Clemens
AU - Weber, Frank
AU - Wiendl, Heinz
AU - Wildemann, Brigitte
AU - Zettl, Uwe K
AU - Ziemann, Ulf
AU - Zipp, Frauke
AU - Arloth, Janine
AU - Weber, Peter
AU - Radivojkov-Blagojevic, Milena
AU - Scheinhardt, Markus O
AU - Dankowski, Theresa
AU - Bettecken, Thomas
AU - Lichtner, Peter
AU - Czamara, Darina
AU - Carrillo-Roa, Tania
AU - Binder, Elisabeth B
AU - Berger, Klaus
AU - Bertram, Lars
AU - Franke, Andre
AU - Gieger, Christian
AU - Herms, Stefan
AU - Homuth, Georg
AU - Ising, Marcus
AU - Jöckel, Karl-Heinz
AU - Kacprowski, Tim
AU - Kloiber, Stefan
AU - Laudes, Matthias
AU - Lieb, Wolfgang
AU - Lill, Christina M
AU - Lucae, Susanne
AU - Meitinger, Thomas
AU - Moebus, Susanne
AU - Müller-Nurasyid, Martina
AU - Nöthen, Markus M
AU - Petersmann, Astrid
AU - Rawal, Rajesh
AU - Schminke, Ulf
AU - Strauch, Konstantin
AU - Völzke, Henry
AU - Waldenberger, Melanie
AU - Wellmann, Jürgen
AU - Porcu, Eleonora
AU - Mulas, Antonella
AU - Pitzalis, Maristella
AU - Sidore, Carlo
AU - Zara, Ilenia
AU - Cucca, Francesco
AU - Zoledziewska, Magdalena
AU - Ziegler, Andreas
AU - Hemmer, Bernhard
AU - Müller-Myhsok, Bertram
PY - 2016/6
Y1 - 2016/6
N2 - 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.
AB - 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.
U2 - 10.1126/sciadv.1501678
DO - 10.1126/sciadv.1501678
M3 - SCORING: Journal article
C2 - 27386562
VL - 2
SP - e1501678
JO - SCI ADV
JF - SCI ADV
SN - 2375-2548
IS - 6
ER -