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Role of genetic susceptibility variants in predicting clinical course in multiple sclerosis: a cohort study

Citation

Pan, G and Simpson Jr, S and van der Mei, I and Charlesworth, JC and Lucas, R and Ponsonby, A-L and Zhou, Y and Wu, F and Taylor, BV, AusLong/Ausimmune Investigator Group, Role of genetic susceptibility variants in predicting clinical course in multiple sclerosis: a cohort study, Journal of Neurology, Neurosurgery and Psychiatry, 87, (11) pp. 1204-1211. ISSN 0022-3050 (2016) [Refereed Article]

Copyright Statement

Copyright 2016 The Author(s)

DOI: doi:10.1136/jnnp-2016-313722

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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Pan, G (Mr Gongbu Pan)
Author:Simpson Jr, S (Dr Steve Simpson JR)
Author:van der Mei, I (Associate Professor Ingrid van der Mei)
Author:Charlesworth, JC (Dr Jac Charlesworth)
Author:Zhou, Y (Mr Yuan Zhou)
Author:Wu, F (Mr Feitong Wu)
Author:Taylor, BV (Professor Bruce Taylor)
ID Code:111099
Year Published:2016
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-08-30
Last Modified:2017-11-06
Downloads:0

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