Searching for MS Susceptibility Genes
Ending MS can’t come fast enough and one key to ending MS is our focus on genetics. Research suggests that MS occurs in individuals and in families whose genes make them susceptible to developing the disease, and that many genes contribute to MS susceptibility. In addition, individuals who are genetically at risk must encounter some other triggering factor
in the environment to actually develop MS. Pinpointing the exact location of these “MS genes” could help determine who is at risk for developing the disease, and may provide clues to its cause, prevention and better treatment.
Genetics is an important research issue in MS 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 before it appears.
Focusing on Genetics with Worldwide Collaboration
With early seed funding from a National MS Society Collaborative MS Research Center Award, MS researchers from around the world have joined forces to create the International MS Genetics Consortium, whose work has already sped the search for MS genes exponentially. In 2007 the Consortium published a groundbreaking initial genome-wide study that clearly identified two new genes (representing only the 2nd and 3rd susceptibility genes identified overall at that time) that predispose people to developing MS.
That work demonstrated that this approach could successfully identify important MS genes, but also made it apparent that much larger studies would be necessary to identify most of the remaining common MS susceptibility genes. The Consortium expanded to include more groups from more countries, forming the basis for a grant from The Wellcome Trust to perform such a study. They then identified 29 new genetic variants associated with MS, and confirmed 23 others previously associated with the disease, verifying a major role for the immune system in the development of MS. Read more
The team then identified 48 new genetic variants associated with MS, bringing the total number of genetic variants that may influence susceptibility to MS to 110. The study involved nearly 30,000 people with MS and more than 50,000 controls without MS, and was funded by more than 40 agencies and foundations, including the Wellcome Trust, the National Institutes of Health, and the National MS Society. Read more
Genes identified in this study are being confirmed and expanded in an independent, second large-scale set of cases with a research grant from the Society.
Genetics differences between African-Americans and Caucasian-Americans: A nationwide team of researchers has conducted the largest genetic study of people with MS of non-European ancestry, screening for known gene variants in more than 1,000 African Americans with MS, and showing significant differences from white Americans. These differences may help explain differences in disease incidence and activity that are observed between African-Americans and white Americans. Read more
A blood test for MS? The disease course in MS and the response to therapy vary from person to person, and there is currently no reliable means to tell early on how active any individual’s MS is likely to be. A team led by Philip L. De Jager, MD, a Harry Weaver Scholar of the National MS Society (Harvard’s Brigham and Women’s Hospital, Boston) has discovered that differences in active genes – detectable in blood samples – has the potential to be used to group people with MS into categories that predict disease course and response to therapy. Further research is needed to verify and refine this approach before it becomes a tool that can benefit treatment decisions made by people with MS and their health care providers. Read more
The National MS Society through Fast Forward, and Lineagen, Inc., an innovative molecular diagnostics company focused on complex, genetically linked disorders, are funding the clinical development and validation of a blood-based test for MS. The goal of the program is to develop a test that can aid clinicians in diagnosing MS, distinguishing it from other neurological disorders, and providing the prognostic information needed to help guide treatment decisions and response to therapies. Read more
Gene-environment interactions: Studying human cells isolated in the laboratory, researchers revealed a novel interaction between two genes that influence susceptibility to developing MS, certain environmental factors, and a chemical process (called N-glycosylation) that modifies the structure of molecules, which together may contribute to our understanding of how complex interactions lead to the development of MS. Read more