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Multiple Sclerosis Genome Wide Association Study (MSGWAS)

DAS Compston

Leena Peltonen, Stephen L Hauser, David A Halfer, Stephen J Sawcer.

Multiple sclerosis is the most common potentially disabling neurological condition affecting young adults in the developed world. The health, social and economic costs are considerable. Initially the course is relapsing and remitting, but a high proportion of those affected eventually become disabled due to disease progression; and for many this is the harbinger of disintegration in their personal and professional lifestyles. Despite important advances in therapeutics, none of the currently available disease-modifying drugs provide long-term benefits. Undoubtedly, the greatest barrier to the development of more successful treatments is our poor understanding of pathogenesis and disease mechanisms. The available evidence suggests that multiple sclerosis is primarily an autoimmune disease in which inflammation initiates a secondary neurodegenerative process. However, little is known about events that trigger the disease or factors that govern its highly variable course and severity.

We aim to identify genetic variants influencing susceptibility to multiple sclerosis by performing an extensive genome-wide association study (GWAS) in an exceptionally well characterised study sample derived from multiple populations having a high prevalence of the disease in which we expect ubiquitous susceptibility factors to be represented. We will use these same data to characterise genetic variants influencing the severity and clinical course of the disease.

This application is submitted on behalf of the International Multiple Sclerosis Genetics Consortium (IMSGC) and the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) collaborative group. Together, these consortia include 18 research groups with synergistic expertise, who between them have access to a critical mass in terms of DNA samples from phenotyped individuals with multiple sclerosis. We propose to perform an extensive GWAS in 10,000 cases and compare these with data from existing population-specific control cohorts, including those provided by WTCCC. Ultimately we will combine these new data with other GWAS being performed in multiple sclerosis including the smaller GWAS we have already published.