Sep 30, 2013
In the largest study of its kind, a global collaboration of scientists has identified 48 new genetic variants associated with MS, bringing the total number of genetic variants that may influence susceptibility to MS to 110. These findings do not substantially improve the ability to provide genetic counseling to individuals, but should add knowledge about complex biological pathways that lead to the development of MS. 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. Nearly 200 investigators of the International MS Genetics Consortium, representing 13 countries, published in Nature Genetics (published online, September 29, 2013). 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 National MS Society.
Background: MS is believed to occur in people whose genes make them susceptible to whatever triggers the disease (Read more). In order to end MS, we need to understand the genetic roots of the disease.
The International MS Genetics Consortium (IMSGC) was formed with funding from the National MS Society to take advantage of advancing technology making it possible to conduct Genome-Wide Association Study (GWAS). In 2007 the Consortium published a groundbreaking initial GWAS 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 the GWAS 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 its 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 here).
The Study: To conduct this study, research groups in 13 countries studied DNA samples from 29,300 individuals with MS, and 50,794 unrelated controls without MS. Using sophisticated array-based genotyping technology, the team identified 48 new genetic associations to MS and confirmed 49 genetic associations to MS that had been suggested previously.
The team went on to perform statistical analyses to look for immune system-related function among the genes near these associated variants. They found that the strongest association was related to a gene that has been shown to activate a molecule called “nuclear factor kappa B.” This is a signaling molecule that has an important role in controlling the gene activity involved in inflammation.
The next step will be to replicate and extend the findings emerging from this study. This effort is being made possible with a research grant from the National MS Society, funded in part by a lead gift from Richard Slifka to the National MS Society’s Greater New England Chapter.
This confirmation is critical because comparisons of large data sets while increasing our chance of finding even the genes of moderate effect, always require further replication and more detailed examination. Moreover, in this study, immune system activity will be studied in new participants identified, allowing for a better understanding of the functional relevance of the genes associated with the occurrence of MS.
Conclusion: These latest gene findings promise to better define the biological pathways leading to MS, which may ultimately lead to ways to prevent the disease and enhance our ability to design better treatments. The genetics studies of the IMSGC are a great example of how the Society is helping to drive global collaborations and research to end MS. Read more about genetics research funded by the National MS Society, and read about opportunities to participate in this exciting research.