Researchers uncover 48 new genetic variants associated with multiple sclerosis

Scientists of the International Multiple Sclerosis Genetics Consortium (IMSGC) have identified an additional 48 genetic variants influencing the risk of developing multiple sclerosis. This work, for which the University of Cambridge led the UK’s contribution, nearly doubles the number of known genetic risk factors and thereby provides additional key insights into the biology of this debilitating neurological condition.

The genes implicated by the newly identified associations underline the central role played by the immune system in the development of multiple sclerosis and show substantial overlap with genes known to be involved in other autoimmune diseases.

The study, published online yesterday in the journal Nature Genetics, is the largest investigation of multiple sclerosis genetics to date.

Multiple sclerosis (MS) is a chronic disabling neurological condition that affects over 2.5 million individuals worldwide. The disease results in patchy inflammation and damage to the central nervous system that causes problems with mobility, balance, sensation and cognition depending on the location of the changes. Neurological symptoms are often intermittent in the early stages of the disease but tend to become persistent and progressively worsen with the passage of time for the majority of patients.

The risk of developing multiple sclerosis is increased in those who have a family history of the disease. Research studies in twins and adopted individuals have shown that this increased risk is primarily the result of genetic risk factors. The findings announced today nearly double the number of confirmed susceptibility loci, underlining the critical role played by the immune system in the development of multiple sclerosis, and highlighting the marked similarities between the genetic architecture underlying susceptibility to this and the many other autoimmune diseases.

The present study takes advantage of custom designed technology known as ImmunoChip - a high-throughput genotyping array specifically designed to interrogate a targeted set of genetic variants linked to one or more autoimmune diseases. IMSGC researchers used the ImmunoChip platform to analyze the DNA from 29,300 individuals with multiple sclerosis and 50,794 unrelated healthy controls, making this the largest genetics study ever performed for multiple sclerosis.

In addition to identifying 48 new susceptibility variants, the study also confirmed and further refined a similar number of previously identified genetic associations. With these new findings, there are now 110 genetic variants associated with MS. Although each of these variants individually confers only a very small risk of developing multiple sclerosis, collectively they explain approximately 20% of the genetic component of the disease.

Led by the University of Miami Miller School of Medicine, this study relied upon an international team of 193 investigators from 84 research groups in 13 countries. The work was funded by more than 40 local and national agencies and foundations.

Commenting on the significance of the work and the nature of the collaboration, University of Miami’s Dr. Jacob McCauley who, on behalf of the IMSGC, led the study, explained: “With the release of these new data, our on-going effort to elucidate the genetic components of this complex disease has taken a major step forward. Describing the genetic underpinnings of any complex disease is a complicated but critical step. By further refining the genetic landscape of multiple sclerosis and identifying novel genetic associations, we are closer to being able to identify the cellular and molecular processes responsible for MS and therefore the specific biological targets for future drug treatment strategies. These results are the culmination of a thoroughly collaborative effort. A study of this size and impact is only possible because of the willingness of so many hard working researchers and thousands of patients to invest their time and energy in a shared goal.”

Research in the UK is led by Professor Alastair Compston, a co-founder of the International Multiple Sclerosis Genetics Consortium, and Professor Stephen Sawcer, each from the Department of Clinical Neurosciences at the University of Cambridge. Describing the work Professor Sawcer commented: “This is another excellent example of the power of international collaboration. Each of the new associations brings nearer an understanding of how multiple sclerosis develops and thereby closer to our ultimate goal of a rational therapy that is both safe and effective at all stages of the disease.”

The International Multiple Sclerosis Genetics Consortium was founded in 2003 and now involves multiple sclerosis and genetics researchers from around the world who coordinate their activities in the belief that this is the way to understand the origins of multiple sclerosis and apply that knowledge to improve the treatment of people at risk of this potentially disabling disease.