Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

Autor: Uwe K. Zettl, Michael Pütz, Rajesh Rawal, Frauke Zipp, Martin Stangel, Ulf Schminke, Marcus Ising, Martina Müller-Nurasyid, Heinz Wiendl, Jürgen Haas, Thomas Meitinger, Michael Hecker, Wolfgang Lieb, Magdalena Zoledziewska, Tania Carrillo-Roa, Ulf Ziemann, S. Nischwitz, Stefan Herms, Maristella Pitzalis, Stefan Kloiber, Frank Weber, Hayrettin Tumani, Bertram Müller-Myhsok, Sven G. Meuth, Georg Homuth, Ralf Gold, M. Knop, Antonella Mulas, Christina M. Lill, Henry Völzke, Antonios Bayas, Francesco Cucca, Eleonora Porcu, Andrew T. Chan, Janine Arloth, Lukas Bechmann, Darina Czamara, Dorothea Buck, Klaus Berger, Peter Lichtner, Jürgen Wellmann, Susanne Moebus, Andre Franke, Florian Then Bergh, Peter Weber, Thomas Bettecken, Ilenia Zara, Till F. M. Andlauer, Volker Limmroth, Achim Berthele, Ralf A. Linker, Tobias Ruck, Anke Salmen, Matthias Laudes, Gisela Antony, Christiane Graetz, Christian Gieger, Konstantin Strauch, Astrid Petersmann, Elisabeth B. Binder, Melanie Waldenberger, Christiane Gasperi, Carlo Sidore, Brigitte Wildemann, Friedemann Paul, Felix Luessi, Bernhard Hemmer, Klarissa Hanja Stürner, Karl-Heinz Jöckel, Milena Radivojkov-Blagojevic, Björn Tackenberg, Tim Kacprowski, Lars Bertram, Clemens Warnke, Markus O. Scheinhardt, Theresa Dankowski, Verena Loleit, Tania Kümpfel, Carmen Infante-Duarte, Susanne Lucae, Markus M. Nöthen, Jan-Patrick Stellmann, Mark Mühlau, Andreas Ziegler
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
DLEU1
Medizin
Genome-wide association study
Epigenesis
Genetic
Cohort Studies
Research Articles
Transcriptional Regulator ERG
Genetics
Aged
80 and over
Glycine Hydroxymethyltransferase
education.field_of_study
Multidisciplinary
DNA methylation
SciAdv r-articles
Middle Aged
SHMT1
3. Good health
ddc
DNA-Binding Proteins
ERG
Female
MAZ
Function and Dysfunction of the Nervous System
Research Article
Adult
Adolescent
Population
Quantitative Trait Loci
610 Medicine & health
Dleu1
Dna Methylation
Erg
L3mbtl3
Maz
Multiple Sclerosis
Shmt1
Genome-wide Association Study
Quantitative trait locus
Biology
Major histocompatibility complex
Neurological Disorders
Multiple sclerosis
03 medical and health sciences
Young Adult
Humans
Genetic Predisposition to Disease
L3MBTL3
Epigenetics
Allele
education
Alleles
Aged
genome-wide association study
030104 developmental biology
Genetic Loci
Case-Control Studies
biology.protein
Transcription Factors
Zdroj: Sci. Adv. 2:e1501678 (2016)
Science advances
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; ... (2016). Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation. Science Advances, 2(6), e1501678. American Association for the Advancement of Science 10.1126/sciadv.1501678
Science Advances
ISSN: 2375-2548
DOI: 10.1126/sciadv.1501678
Popis: Genome-wide study in Germans identifies four novel multiple sclerosis risk genes and confirms already known gene loci.
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.
Databáze: OpenAIRE
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