Montreal Heart Institute
A large-scale genomic study has uncovered new genetic variations associated with multiple sclerosis (MS); findings that suggest a possible link between MS and other autoimmune diseases. The study, led by an international consortium of clinical scientists and genomics experts, is the first comprehensive study investigating the genetic basis of MS. These findings appear in the July 29 online edition of the New England Journal of Medicine.
MS, a disease of the central nervous system whose symptoms range from mild muscle weakness to partial or complete paralysis, is widely considered an autoimmune disease, one that arises from a combination of genetic and environmental factors. This collusion of events leads the body to attack and destroy the insulation along nerve fibers. This study, which analyzed genomic information from 12,360 people, confirmed that immune system genes are altered in people diagnosed with MS, and pointed to potential mechanisms of the disease.
The researchers gathered 931 sets of DNA samples from MS patients and their parents. They analyzed approximately 500,000 single nucleotide polymorphisms (SNPs), that is, small differences in DNA sequence that represent the most common genetic variations between individuals, and looked for variations that were more commonly inherited by people with MS compared to samples from people without the disease. To double-check the findings, they performed a second analysis of other sets of families, individual cases of MS, and a control group. In the end, all the samples were combined for a final analysis of more than 12,000 subjects.
The only genetic link for MS previously identified using other techniques is in the major histocompatibility complex (MHC), a large cluster of genes responsible for many immune functions, including preventing the body's immune cells from attacking its own tissues. This analysis confirmed that link but went further to find other variants in genetic regions that are more common in people with MS.
One of the regions contains a gene called the IL-2 receptor, which has also been linked to two other autoimmune diseases; type 1 diabetes and autoimmune thyroid disease.
"Scientists are increasingly finding genetic links between immune-mediated diseases that affect different tissues in the body, including type one diabetes, Crohn's disease, psoriasis, and rheumatoid arthritis," says Dr. John D. Rioux, PhD, Associate Professor of Medicine at the Montreal Heart Institute and the Université de Montréal, one of the study's authors. "This study will likely spur further research into the connection between these seemingly separate conditions."
Another region harbors a gene called the IL-7 receptor, which helps to control the activity of a class of immune cells called regulatory T cells. Two papers appearing simultaneously in Nature Genetics confirm this finding, and explore how the change in the IL-7 receptor affects the immune system. "I believe that this receptor and its interaction with regulatory T cells will now become a major focus of research on MS," says Stephen Hauser, professor of neurology at University of California San Francisco, and another author on the paper.
"One of the most encouraging outcomes of this current genomic study," says David Hafler, the Jack, Sadie and David Breakstone professor neurology at Harvard Medical School and Brigham and Women's Hospital, "is that it is helping us to pin point genes that may elevate the risk of developing MS and other autoimmune diseases pointing the way to new areas of research and therapeutic targets to both treat and eventually prevent these diseases." "This study illustrates the power of collaboration", added Dr. Rioux.
"Individually, none of us could have completed a study of this scale and complexity. In an effort to see the work extended, we are now committed to making the entire data set available to MS researchers worldwide."
This work was supported by grants from the US National Multiple Sclerosis Society, the U.S. National Institutes of Health, and the Penates Foundation. A complete list of authors and their affiliations can be found below.