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; ... (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

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Chan, Andrew and Salmen, Anke

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2375-2548

Publisher:

American Association for the Advancement of Science

Language:

English

Submitter:

Stefanie Hetzenecker

Date Deposited:

27 Jul 2016 10:27

Last Modified:

27 Jul 2016 10:27

Publisher DOI:

10.1126/sciadv.1501678

PubMed ID:

27386562

Uncontrolled Keywords:

DLEU1; DNA methylation; ERG; L3MBTL3; MAZ; Multiple sclerosis; SHMT1; genome-wide association study

BORIS DOI:

10.7892/boris.84401

URI:

https://boris.unibe.ch/id/eprint/84401

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