Summary: Researchers have identified four new genes that appear to be altered in patients with Multiple Sclerosis.
Source: TUM.
Indications of an interplay between genetic and environmental factors.
Scientists of the Technical University of Munich (TUM) and the Max Planck Institute of Psychiatry have identified four new risk genes that are altered in German patients with multiple sclerosis (MS). The results point to a possible involvement of cellular mechanisms in the development of the disease, through which environmental influences affect gene regulation. The research project was supported by the German Competence Network Multiple Sclerosis (KKNMS).
The newly identified regions in the human genome associated with the disease improve our model of how MS develops. “All four genes are important for regulatory processes within immune cells. Interestingly, they are linked to epigenetic mechanisms. These are bookmarks in the genome that are placed by environmental influences and control the expression of genes”, explains Prof. Dr. Bernhard Hemmer, Director of the Clinic and Policlinic for Neurology at TUM’s Klinikum rechts der Isar and Spokesman of the Executive Board of the KKNMS.
Epigenetic signals mark DNA sequences in human cells and are critical for regulating which of the approximately 20,000 genes inside a cell get activated. These signals are programmed by environmental influences throughout a person’s lifetime. One of the genes identified, named SHMT1, plays a central role in DNA methylation, one of the most important epigenetic regulatory mechanisms.
“Environmental factors strongly contribute to the disease”
The findings expand our understanding of the extent to which genetic influences play a part in the development of MS: “Because the hereditary component in developing MS is limited, environmental factors strongly contribute to the disease. They can influence the activity of MS-relevant genes via epigenetic mechanisms. We have now discovered indicators for regulation of methylation being a potential interface where genetic and environmental MS risk factors interact”, says Prof. Dr. Bertram Müller-Myhsok, Research Group Leader Statistical Genetics at the Max Planck Institute of Psychiatry.
The largest genetic MS study carried out in a single country
Not only did the scientists identify four new risk genes in the German population, but they also confirmed the existence of a dozen previously identified genes. In contrast to earlier studies, they took a new methodological approach: instead of examining a large number of international samples from different ethnic groups, the scientists focused on a single population of genetically homogeneous German patients. This allowed them to identify risk genes that had so far not been discovered in international studies. With just under 5,000 patients and a sample of over 10,000 healthy people, this is the largest genetic MS study carried out in a single country to date. The study has been published in the current edition of the journal Science Advances.
Multiple Sclerosis is an inflammatory disease of the central nervous system. With about 200,000 people affected in Germany alone, it is one of the most common neurological diseases among young adults. In the majority of cases, MS is a relapsing-remitting disease that causes a wide range of symptoms, including visual disturbances, paralysis, numbness, and dizziness. Its cause remains unknown.
Funding: The research project was supported by the German Competence Network Multiple Sclerosis (KKNMS).
Source: Paul Hellmich – TUM
Image Source: This NeuroscienceNews.com image is credited to Ktsdesign.
Original Research: Abstract for “Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation” by Till F. M. Andlauer, Dorothea Buck, Gisela Antony, Antonios Bayas, Lukas Bechmann, Achim Berthele, Andrew Chan, Christiane Gasperi, Ralf Gold, Christiane Graetz, Jürgen Haas, Michael Hecker, Carmen Infante-Duarte, Matthias Knop, Tania Kümpfel, Volker Limmroth, Ralf A. Linker, Verena Loleit, Felix Luessi, Sven G. Meuth, Mark Mühlau, Sandra Nischwitz, Friedemann Paul, Michael Pütz, Tobias Ruck, Anke Salmen, Martin Stangel, Jan-Patrick Stellmann, Klarissa H. Stürner, Björn Tackenberg, Florian Then Bergh, Hayrettin Tumani, Clemens Warnke, Frank Weber, Heinz Wiendl, Brigitte Wildemann, Uwe K. Zettl, Ulf Ziemann, Frauke Zipp, Janine Arloth, Peter Weber, Milena Radivojkov-Blagojevic, Markus O. Scheinhardt, Theresa Dankowski, Thomas Bettecken, Peter Lichtner, Darina Czamara, Tania Carrillo-Roa, Elisabeth B. Binder, Klaus Berger, Lars Bertram, Andre Franke, Christian Gieger, Stefan Herms, Georg Homuth, Marcus Ising, Karl-Heinz Jöckel, Tim Kacprowski, Stefan Kloiber, Matthias Laudes, Wolfgang Lieb, Christina M. Lill, Susanne Lucae, Thomas Meitinger, Susanne Moebus, Martina Müller-Nurasyid, Markus M. Nöthen, Astrid Petersmann, Rajesh Rawal, Ulf Schminke, Konstantin Strauch, Henry Völzke, Melanie Waldenberger, Jürgen Wellmann, Eleonora Porcu, Antonella Mulas, Maristella Pitzalis, Carlo Sidore, Ilenia Zara, Francesco Cucca, Magdalena Zoledziewska, Andreas Ziegler, Bernhard Hemmer and Bertram Müller-Myhsok in Science Advances. Published online June 17 2016 doi:10.1126/sciadv.1501678
[cbtabs][cbtab title=”MLA”]TUM. “Four New Risk Genes For Multiple Sclerosis Discovered.” NeuroscienceNews. NeuroscienceNews, 20 June 2016.
<https://neurosciencenews.com/genetics-multiple-sclerosis-risk-4516/>.[/cbtab][cbtab title=”APA”]TUM. (2016, June 20). Four New Risk Genes For Multiple Sclerosis Discovered. NeuroscienceNews. Retrieved June 20, 2016 from https://neurosciencenews.com/genetics-multiple-sclerosis-risk-4516/[/cbtab][cbtab title=”Chicago”]TUM. “Four New Risk Genes For Multiple Sclerosis Discovered.” https://neurosciencenews.com/genetics-multiple-sclerosis-risk-4516/ (accessed June 20, 2016).[/cbtab][/cbtabs]
Abstract
Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation
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.
“Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation” by Till F. M. Andlauer, Dorothea Buck, Gisela Antony, Antonios Bayas, Lukas Bechmann, Achim Berthele, Andrew Chan, Christiane Gasperi, Ralf Gold, Christiane Graetz, Jürgen Haas, Michael Hecker, Carmen Infante-Duarte, Matthias Knop, Tania Kümpfel, Volker Limmroth, Ralf A. Linker, Verena Loleit, Felix Luessi, Sven G. Meuth, Mark Mühlau, Sandra Nischwitz, Friedemann Paul, Michael Pütz, Tobias Ruck, Anke Salmen, Martin Stangel, Jan-Patrick Stellmann, Klarissa H. Stürner, Björn Tackenberg, Florian Then Bergh, Hayrettin Tumani, Clemens Warnke, Frank Weber, Heinz Wiendl, Brigitte Wildemann, Uwe K. Zettl, Ulf Ziemann, Frauke Zipp, Janine Arloth, Peter Weber, Milena Radivojkov-Blagojevic, Markus O. Scheinhardt, Theresa Dankowski, Thomas Bettecken, Peter Lichtner, Darina Czamara, Tania Carrillo-Roa, Elisabeth B. Binder, Klaus Berger, Lars Bertram, Andre Franke, Christian Gieger, Stefan Herms, Georg Homuth, Marcus Ising, Karl-Heinz Jöckel, Tim Kacprowski, Stefan Kloiber, Matthias Laudes, Wolfgang Lieb, Christina M. Lill, Susanne Lucae, Thomas Meitinger, Susanne Moebus, Martina Müller-Nurasyid, Markus M. Nöthen, Astrid Petersmann, Rajesh Rawal, Ulf Schminke, Konstantin Strauch, Henry Völzke, Melanie Waldenberger, Jürgen Wellmann, Eleonora Porcu, Antonella Mulas, Maristella Pitzalis, Carlo Sidore, Ilenia Zara, Francesco Cucca, Magdalena Zoledziewska, Andreas Ziegler, Bernhard Hemmer and Bertram Müller-Myhsok in Science Advances. Published online June 17 2016 doi:10.1126/sciadv.1501678
