Searching for MS Genes

Ending MS can’t come fast enough and one key to ending MS is our focus on genes that help make people susceptible to developing MS. Research suggests that MS occurs in individuals and in families whose genes make them susceptible, and that many genes contribute to MS susceptibility. In addition, individuals who are genetically at risk must encounter some other triggering factor or factors in their environment to actually develop MS.

Pinpointing and understanding “MS genes” is important because
• it will provide key information regarding the cause of the disease and therefore how to prevent it
• genes that are associated with MS may be targets for the development of new therapies
• if we could identify those people who have a strong genetic predisposition to the disease, we might be able to intervene at its earliest stages or prevent MS.

The MS DNA Bank
With funding from the National MS Society, the University of California at San Francisco established a DNA bank in 1997 that spearheaded multiple successful collaborations to identify variants in the genome that influence the individual’s risk to develop multiple MS. With further Society funding, the DNA Bank is now maintaining and expanding its core DNA repository of MS patients, family members and unrelated controls, linking it to a sophisticated database for the storage of detailed clinical, demographic, and laboratory data. This Bank provides an outstanding opportunity to identify and characterize MS-related genes, which may translate into clinically useful genetic biomarkers and reveal novel targets for new therapies. You can participate in these genetic studies. Please note: these studies cannot enroll international participants at this time.

The International MS Genetics Consortium
The next generation of MS genetics began when the International MS Genetics Consortium (IMSGC) was launched with early seed funding from a National MS Society Collaborative MS Research Center Award. The IMSGC comprises the world’s top neurologists and geneticists. In 2007, the IMSGC published a groundbreaking initial genome-wide study that clearly identified two new genes that predispose people to developing MS. Just 12 years later, the IMSGC has published the largest MS genetics study to date, analyzing data from 47,429 people with MS and 68,374 individuals without MS. They confirmed 233 variations in the human genome that contribute to the risk of developing MS. The variations were found to influence many different immune cell types and tissues, indicating that broad dysfunction in the immune system underlies the onset of MS. These teams could not have accomplished this massive task if not for this international collaboration.

• Interpreting the genetic variations identified by the IMSGC and other large-scale studies remains a challenge. A team at Yale is seeking to fine tune MS genetic studies using a novel framework that combines MS genetics data with similar data from related diseases, for insight into disease mechanisms and possible gene regulation.

• Predicting MS risk: The variants identified by the IMSGC do not explain all of the risk of developing MS, indicating the need for further research to investigate less common genetic variants that might help to fill this gap. In subsequent work, members identified four novel genes containing rare variants — those with a frequency below 1 percent in the general population — that contribute to the risk of developing MS. 

• The interaction of genes and environmental factors is being investigated: A team at University of California, Berkeley is using a novel, web-based tool to study the influence of genetic, environmental and other clinical factors in hundreds of people with MS to help further understand why some develop worse cognitive function and physical disability.

• Focusing on ethnic groups with varying levels of susceptibility to MS may help to understand the clinical differences between ethnic groups, and help pinpoint regions that contain MS genes. Researchers reported that two genetic variants involved in regulating immune responses may explain the increased risk of multiple sclerosis in African Americans who have European ancestors. The authors comment that it is likely that these genes combine with other genetic and environmental factors to explain what is often a worse clinical experience of MS in African Americans. Researchers are now funded by the Society to establish a unique dataset containing demographic, neurologic, and genetic material from a large cohort of Hispanic Latinos with MS. They are examining known genes that influence MS and looking for new genes that may be involved in MS specifically in the Hispanic population.Join this effort