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Genotype-phenotype correlation for non-HLA disease associated risk alleles in multiple sclerosis

Harding, Katharine, Ingram, Gillian, Cossburn, Mark D., Hirst, Claire Louise, Pickersgill, Trevor, Ben-Shlomo, Yoav and Robertson, Neil 2012. Genotype-phenotype correlation for non-HLA disease associated risk alleles in multiple sclerosis. Neuroscience Letters 526 (1) , pp. 15-19. 10.1016/j.neulet.2012.06.040

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Abstract

Background Recent advances in MS genetics have led to the successful identification of a number of novel disease associated non-HLA genes. It is now becoming possible to begin to analyse the possible effects of these genes on aspects of disease phenotype where longitudinal clinical data is available. Objective We examined phenotypic impact of 10 non-HLA disease associated single nucleotide polymorphisms (SNPs) in 1003 patients with MS followed for an average of 14.1 years. Methods Association of SNPs with time to established disability milestones (Expanded Disability Status Scale (EDSS) 4.0, 6.0, 8.0), onset of secondary progression and cross-sectional aspects of early phenotype were tested using survival analysis. Results No SNP was associated with systematic deflection in time to disability milestones, age at onset or time to secondary progression. Conclusions Genotypic information from non-HLA associated SNPs is unlikely to inform individual patient prognosis in the clinical setting although minor phenotypic effects operative at specific phases of disease cannot be excluded. This preliminary study provides a framework for future genotype–phenotype analysis in MS and will need to be replicated in independent patient cohorts.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: multiple sclerosis, prognosis, genetics
Publisher: Elsevier
ISSN: 0304-3940
Last Modified: 11 Jun 2019 20:24
URI: http://orca-mwe.cf.ac.uk/id/eprint/41261

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