Epigenetic genes linked to multiple sclerosis risk in large-scale study

Written by Sonia Mannan

Scientists at the Technical University of Munich and the Max Planck Institute of Psychiatry (both Munich, Germany) have conducted a genome-wide association study on multiple sclerosis (MS) susceptibility. This led to the discovery of four new risk genes that were modified in patients with MS, indicating that these genes, which govern epigenetic processes, may play a part in the cellular mechanisms in MS development. The study was published in the journal Science Advances.
As the cause of MS is not yet understood, this new discovery of the four risk genes, termed L3MBTL3, MAZ, ERG and SHMT1, may facilitate a better understanding of how the disease develops. Bernhard Hemmer (Technical University of Munich) explained, “All four genes are important for regulatory processes within immune cells. Interestingly, they are linked to epigenetic mechanisms. These are bookmarks in the genome that are placed by environmental influences and control the expression of genes.”

SHMT1 is one of the four genes identified and is involved in DNA methylation, which is a vital epigenetic regulatory mechanism. “Because the hereditary component in developing MS is limited, environmental factors strongly contribute to the disease. They can influence the activity of MS-relevant genes via epigenetic mechanisms. We have now discovered indicators for regulation of methylation being a potential interface where genetic and environmental MS risk factors interact,” commented Bertram Müller-Myhsok (Max Planck Institute of Psychiatry).

This study was the largest genetic MS study to date, with almost 5000 patients and a sample of more than 10,000 healthy individuals. Notably, this study differed from previous studies in that the focus was on German patients only rather than a variety of ethnic groups. This was to provide genetic homogeneity and identify risk genes not previously discovered.

As well as the four new risk genes, the study confirmed the existence of many other previously identified genes. The researchers hope that the outcome of the study will provide a better understanding of how environmental influences affect gene regulation in the pathogenesis of MS.

Sources: Andlauer TFM, Buck D, Antony G et al. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation. Sci. Adv. 2(6), e1501678 (2016); www.tum.de/die-tum/aktuelles/pressemitteilungen/kurz/article/33179/