An endophenotype is a concept that allows the description of complex diseases with genetic and environmental contributions,enabling the identification of an at risk population. I aim to describe an endophenotypic gradient between healthy controls, siblings of people with MS and people with MS. Siblings of people with MS are at increased risk of developing MS; this is thought to be a result of genetic and environmental contributions. Epidemiological studies have identified a number of factors contributing to MS risk including smoking,vitamin D,infection with Epstein Barr virus and HLAZDRB1*1501. A genome wide association study in 2011 gave information regarding the contribution of HLAZtype and nonZHLA"SNPs to MS risk. I set out to integrate these into an endophenotypic risk score for MS. When the genetic contribution from HLAZDRB1*1501 alone was used,the mean MS risk score was significantly higher for people with MS than siblings or controls. Siblings had a higher MS risk score than controls. The differences between the three groups become more apparent when all genetic information was used in the MS risk score. I used MRI and biomarker studies to validate the MS risk score generated. Preliminary studies enabled an evaluation of the potential association between selected biomarkers and CSF oligoclonal bands. The analyses performed demonstrate the potential clinical utility of such a score in describing MS risk. Siblings have a risk score intermediate to people with MS and controls, confirming their “at"risk” position in the endophenotype construct. Much of the MS risk in siblings can be attributed to genetics, with environmental factors potentially providing the trigger for clinically apparent disease. The findings of this research have the potential to enrich future prevention studies with individuals at high risk of developing MS,enabling such studies to be performed within a realistic timeframe.