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https://hdl.handle.net/2440/138787
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dc.contributor.author | Pan, G. | - |
dc.contributor.author | Simpson, S. | - |
dc.contributor.author | van der Mei, I. | - |
dc.contributor.author | Charlesworth, J.C. | - |
dc.contributor.author | Lucas, R. | - |
dc.contributor.author | Ponsonby, A.L. | - |
dc.contributor.author | Zhou, Y. | - |
dc.contributor.author | Wu, F. | - |
dc.contributor.author | Taylor, B.V. | - |
dc.contributor.author | Dear, K. | - |
dc.contributor.author | Dwyer, T. | - |
dc.contributor.author | Blizzard, L. | - |
dc.contributor.author | Broadley, S. | - |
dc.contributor.author | Kilpatrick, T. | - |
dc.contributor.author | Williams, D. | - |
dc.contributor.author | Lechner-Scott, J. | - |
dc.contributor.author | Shaw, C. | - |
dc.contributor.author | Chapman, C. | - |
dc.contributor.author | Coulthard, A. | - |
dc.contributor.author | Valery, P. | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Journal of Neurology, Neurosurgery and Psychiatry, 2016; 87(11):1204-1211 | - |
dc.identifier.issn | 0022-3050 | - |
dc.identifier.issn | 1468-330X | - |
dc.identifier.uri | https://hdl.handle.net/2440/138787 | - |
dc.description.abstract | Background: The genetic drivers of multiple sclerosis (MS) clinical course are essentially unknown with limited data arising from severity and clinical phenotype analyses in genome-wide association studies. Methods: Prospective cohort study of 127 first demyelinating events with genotype data, where 116 MS risk-associated single nucleotide polymorphisms (SNPs) were assessed as predictors of conversion to MS, relapse and annualised disability progression (Expanded Disability Status Scale, EDSS) up to 5-year review (ΔEDSS). Survival analysis was used to test for predictors of MS and relapse, and linear regression for disability progression. The top 7 SNPs predicting MS/relapse and disability progression were evaluated as a cumulative genetic risk score (CGRS). Results: We identified 2 non-human leucocyte antigen (HLA; rs12599600 and rs1021156) and 1 HLA (rs9266773) SNP predicting both MS and relapse risk. Additionally, 3 non-HLA SNPs predicted only conversion to MS; 1 HLA and 2 non-HLA SNPs predicted only relapse; and 7 non-HLA SNPs predicted ΔEDSS. The CGRS significantly predicted MS and relapse in a significant, dose-dependent manner: those having ≥5 risk genotypes had a 6-fold greater risk of converting to MS and relapse compared with those with ≤2. The CGRS for ΔEDSS was also significant: those carrying ≥6 risk genotypes progressed at 0.48 EDSS points per year faster compared with those with ≤2, and the CGRS model explained 32% of the variance in disability in this study cohort. Conclusions: These data strongly suggest that MS genetic risk variants significantly influence MS clinical course and that this effect is polygenic. | - |
dc.description.statementofresponsibility | Gongbu Pan, Steve Simpson Jr, Ingrid van der Mei, Jac C Charlesworth, Robyn Lucas, Anne-Louise Ponsonby, Yuan Zhou, Feitong Wu, AusLong/ Ausimmune Investigator Group, Bruce V Taylor ... Keith Dear ... et al. | - |
dc.language.iso | en | - |
dc.publisher | BMJ Publishing Group | - |
dc.rights | © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ | - |
dc.source.uri | http://dx.doi.org/10.1136/jnnp-2016-313722 | - |
dc.subject | Genetic Variation | - |
dc.subject.mesh | Humans | - |
dc.subject.mesh | Multiple Sclerosis, Chronic Progressive | - |
dc.subject.mesh | Multiple Sclerosis, Relapsing-Remitting | - |
dc.subject.mesh | Disease Progression | - |
dc.subject.mesh | Genetic Predisposition to Disease | - |
dc.subject.mesh | HLA Antigens | - |
dc.subject.mesh | Disability Evaluation | - |
dc.subject.mesh | Risk Factors | - |
dc.subject.mesh | Case-Control Studies | - |
dc.subject.mesh | Cohort Studies | - |
dc.subject.mesh | Follow-Up Studies | - |
dc.subject.mesh | Prospective Studies | - |
dc.subject.mesh | Genotype | - |
dc.subject.mesh | Phenotype | - |
dc.subject.mesh | Polymorphism, Single Nucleotide | - |
dc.subject.mesh | Adult | - |
dc.subject.mesh | Middle Aged | - |
dc.subject.mesh | Australia | - |
dc.subject.mesh | Female | - |
dc.subject.mesh | Male | - |
dc.subject.mesh | Genetic Variation | - |
dc.title | Role of genetic susceptibility variants in predicting clinical course in multiple sclerosis: A cohort study | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1136/jnnp-2016-313722 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/544922 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Dear, K. [0000-0002-0788-7404] | - |
Appears in Collections: | Public Health publications |
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