Published in

American Association for the Advancement of Science, Science Advances, 6(2), 2016

DOI: 10.1126/sciadv.1501678

Links

Tools

Export citation

Search in Google Scholar

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

Journal article published in 2016 by Till F. M. Andlauer ORCID, H. Voelzke, H. Vo lzke, Dorothea Buck, Gisela Antony ORCID, Antonios Bayas, Lukas Bechmann, T. Kuempfel, Achim Berthele, Andrew Chan, Andlauer Tf, Christiane Gasperi ORCID, M. Muehlau, Ralf Gold, Christiane Graetz and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Red circle
Postprint: archiving forbidden
Green circle
Published version: archiving allowed
Upload
Policy details
Data provided by SHERPA/RoMEO

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.