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dc.contributor.authorDobson, Ruth
dc.date.accessioned2015-09-21T15:30:57Z
dc.date.available2015-09-21T15:30:57Z
dc.date.issued2013-10
dc.identifier.citationDobson, R. 2013. Towards an endophenotype in multiple sclerosis. Queen Mary University of London.en_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/8779
dc.descriptionPhDen_US
dc.description.abstractAn 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.en_US
dc.description.sponsorshipGuarantors of Brain; ABN/MS Society of Great Britain and Northern Ireland Clinical Research Fellowshipen_US
dc.language.isoenen_US
dc.publisherQueen Mary University of Londonen_US
dc.subjectMedicineen_US
dc.subjectMultiple sclerosisen_US
dc.titleTowards an endophenotype in multiple sclerosisen_US
dc.typeThesisen_US
dc.rights.holderThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author


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    Theses Awarded by Queen Mary University of London

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