International MS Genetics Consortium

As is the case for most neurodegenerative diseases, there is strong evidence to support the idea that MS is a disease with a complex genetic background upon which environmental triggers act. Although many groups have sought to identify these genetic risk factors and many have been proposed, until recently only one risk factor had been reliably identified.

The International MS Genetics Consortium (IMSGC) was formed in 2003 with the specific aim of addressing this challenge. By taking advantage of emerging genetics technology, pooling our patient populations, and sharing financial resources, the IMSGC embarked on a comprehensive  assessment of genetic influences on MS.

With the early support of a few major private donors, the National MS Society, the Penates Foundation and the National Institutes of Health, we collected patient records and DNA samples for thousands of patients, evaluated competing technology platforms and build a large data analysis capacity.

With further funding from the NMSS, the Consortium then undertook a major new analysis of genetic influences on the risk of developing MS. Our combined analysis of 12,360 subjects highlighted a number of possible risk factors. Of these two have been shown to be very significant and are now the subject of major research programs to determine what these genes do and how they influence an individual's risk of developing MS. This work was published in August 2007, in the prestigious New England Journal of Medicine, receiving considerable media attention (Member publications).

Whereas this study highlighted the power of collaboration and the strength of the Consortium, it also confirmed the likelihood that many other MS risk genes exist and will only be revealed by much larger and more powerful studies. Indeed, these advances notwithstanding, knowledge of MS genetics remained incomplete. Collectively, all known risk factors accounted for only 50% of the inherited susceptibility to the disease.

With this in mind the Consortium recently embarked on a major expansion of its genetics program. By more than doubling the number of groups that contribute to the Consortium, and thanks to major funding and support from the UK Wellcome Trust and National MS Society, we are undertaking a new genetics study. In total this study will examine approximately 20,000 patients and 20,000 non-MS control subjects, and will yield more than 24 billion data points.  

The Consortium has identified four sequential elements of this new genetics study of MS:

Phase 1: As of July 2008 the primary genetics scan of the first 10,000 patients and control subjects is underway. Approximately $5 million in funding is in place.

Phase 2: Starting in late 2008 we will begin recruiting a further 10,000 patients to help with this work. $1 million funding is in place.

Phase 3: Starting in the fall of 2009 we will use the newly recruited patients to complete the second and final genetic scan. $1.9 million funding is already in place.

Phase 4: Early 2010 we will start analyzing the massive data set, and identifying new MS risk genes. The funding requirement for this Phase has not yet been finalized.

Once complete, this internationally collaborative project will establish a comprehensive atlas of common genetic variations that affect susceptibility to MS. In addition, the research will identify novel disease candidate genes, pathways and networks, leading to testable hypotheses as to which genes contribute to susceptibility to MS.

The next step will be to use this emerging and more refined model of the causes of MS to direct work in our drug discovery program.

The International MS Genetics Consortium has a formal structure including a small Governance Group, a Strategy Group that directs the day to day research, and a large Members Group.

The Consortium is committed to making all of its data available to any appropriate researcher world wide. Researchers may find out what data is available and how to apply for access by visiting our web site. You can also find out which groups are part of the IMSGC and look at a list of members at www.imsgc.org.

For information on other ways that the Harvard NeuroDiscovery Center is helping beat multiple sclerosis, please visit our MS pages.