ausblenden:
Schlagwörter:
Multiple sclerosis, genome-wide association study, DNA methylation, L3MBTL3, MAZ, ERG, DLEU1, SHMT1
Zusammenfassung:
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.
