genetics

Last reviewed 06/2022

Multiple sclerosis has a complex polygenic inheritance. The genes responsible are not coding for aberrant products but are normally-occuring polymorphisms. Information on the genetics of MS has come from genetic linkage studies of candidates genes, or more recently genome-wide linkage screens.

The main genetic locus for MS (the HLA-DRB1*1501 allele) was discovered in the 1970s within the major histocompatibility complex (MHC) region, long before the era of genome wide association studies.

There is well established linkage with the class II MHC alleles DR15 and DQ6 and the nearby TNF-alpha (1)

A genome wide association study (GWAS) has demonstrated that more than 100 genetic variants influence the risk of multiple sclerosis (MS) (2)

Reference:

• 1) Sawcer S, Maranian M, Setakis E, Curwen V, Akesson E, Hensiek A, Coraddu F, Roxburgh R, Sawcer D, Gray J, Deans J, Goodfellow PN, Walker N, Clayton D, Compston A. "A whole genome screen for linkage disequilibrium in multiple sclerosis confirms disease associations with regions previously linked to susceptibility." Brain 2002 Jun;125(Pt 6):1337-1347
• 2) Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, et al. (2011) Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476: 214-219