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Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

MPS-Authors
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Andlauer,  Till F. M.
Max Planck Institute of Psychiatry, Max Planck Society;

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Knop,  Matthias
Max Planck Institute of Psychiatry, Max Planck Society;

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Nischwitz,  Sandra
Max Planck Institute of Psychiatry, Max Planck Society;

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Weber,  Frank
Max Planck Institute of Psychiatry, Max Planck Society;

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Arloth,  Janine
Max Planck Institute of Psychiatry, Max Planck Society;

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Weber,  Peter
Max Planck Institute of Psychiatry, Max Planck Society;

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Bettecken,  Thomas
Max Planck Institute of Psychiatry, Max Planck Society;

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Czamara,  Darina
Max Planck Institute of Psychiatry, Max Planck Society;

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Carrillo-Roa,  Tania
Max Planck Institute of Psychiatry, Max Planck Society;

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Binder,  Elisabeth B.
Max Planck Institute of Psychiatry, Max Planck Society;

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Ising,  Marcus
Max Planck Institute of Psychiatry, Max Planck Society;

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Kloiber,  Stefan
Max Planck Institute of Psychiatry, Max Planck Society;

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Lucae,  Susanne
Max Planck Institute of Psychiatry, Max Planck Society;

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Müller-Myhsok,  Bertram
Max Planck Institute of Psychiatry, Max Planck Society;

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引用

Andlauer, T. F. M., 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, R. A., Loleit, V., Luessi, F., Meuth, S. G., Muehlau, M., Nischwitz, S., Paul, F., Puetz, M., Ruck, T., Salmen, A., Stangel, M., Stellmann, J.-P., Stuerner, K. H., Tackenberg, B., Bergh, F. T., Tumani, H., Warnke, C., Weber, F., Wiendl, H., Wildemann, B., Zettl, U. K., Ziemann, U., Zipp, F., Arloth, J., Weber, P., Radivojkov-Blagojevic, M., Scheinhardt, M. O., Dankowski, T., Bettecken, T., Lichtner, P., Czamara, D., Carrillo-Roa, T., Binder, E. B., Berger, K., Bertram, L., Franke, A., Gieger, C., Herms, S., Homuth, G., Ising, M., Joeckel, K.-H., Kacprowski, T., Kloiber, S., Laudes, M., Lieb, W., Lill, C. M., Lucae, S., Meitinger, T., Moebus, S., Mueller-Nurasyid, M., Noethen, M. M., 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., & Müller-Myhsok, B. (2016). Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation. SCIENCE ADVANCES, 2(6):. doi:10.1126/sciadv.1501678.


引用: https://hdl.handle.net/11858/00-001M-0000-002C-6706-D
要旨
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.