Multiple sclerosis genome-wide association study (MSGWAS). (360G-Wellcome-084702_Z_08_Z)

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. Given that GWAS genotyping is significantly more cost effective than selected marker genotyping we feel that performing a GWAS in all available cases is scientifically and financially more appropriate that using a staged approach with a modest initial screen followed by attempted replication in unscreened samples. We therefore 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. This extensive screen will provide sufficient power to identify essentially all variants with an Odds Ratio (OR) of > 1.3; 74% of those with an OR of 1.2; and even 24% of those with an OR of just 1.15. Ultimately we will combine these new data with other GWAS being performed in multiple sclerosis including the smaller GWAS we have already published.