4 New ‘Risk Genes’ for Multiple Sclerosis, All Controlling Other Genes, Identified in German Study

In the largest genetic study ever performed in a single country, scientists in Germany discovered four new risk genes for multiple sclerosis (MS). The genes, altered in MS patients, are involved in the control of how other genes are activated through mechanisms known as epigenetics.

The discovery advances understanding of how MS develops as a result of environmental influences, major contributors to the disease.

A huge collaborative effort, involving researchers from the Technical University of Munich (TUM), the Max Planck Institute of Psychiatry, and scientists at more than 50 other, mainly German, research sites, the project was supported by the German Competence Network Multiple Sclerosis (KKNMS).

Researchers recruited 4,888 MS patients and more than 10,000 healthy volunteers, and performed what is known as a genome-wide association study, or GWAS. The method allows scientists to detect risk genes linked to the presence of a certain condition without having any predefined theories on the matter, simply scanning the whole genome for signals that imply an association between a gene and a disease.

Epigenetics involve mechanisms controlling the activity of genes by tagging them with chemical flags that allow or prevent a gene from being transcribed. These flags are not constant, but are attached and removed in response to environmental factors. One of the most widely used flagging mechanisms attaches a methylene chemical group to genes in a process called methylation.

Among the four new risk genes for MS identified in the genetic screen is SHMT1 — a crucial player in DNA methylation contexts.

“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,” Professor Bernhard Hemmer, director of the Clinic and Policlinic for Neurology at TUM, said in a press release.

“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,” said Professor Bertram Müller-Myhsok, the research group leader of Statistical Genetics at the Max Planck Institute of Psychiatry.

In addition to finding the four risk genes, the study, published in the journal Science Advances, might confirm previously identified associations between a dozen other genes and MS risk. The strength of this study, “Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation,” is that, unlike previous large genetic studies, it focused on a purely German population.

This focus gave the scientists genetic material with less variability than that found in international studies involving people of various ethnic backgrounds. Such genetic homogeneity allowed researchers to spot links that become too weak in a mixed group, much as spotting a green hat is easier in a group of people who naturally don black hats.