George, MF and Briggs, FBS and Shao, X and Gianfrancesco, MA and Kockum, I and Harbo, HF and Celius, EG and Bos, SD and Hedstrom, A and Shen, L and Bernstein, A and Alfredsson, L and Hillert, J and Olsson, T and Patsopoulos, NA and De Jager, PL and Oturai, AB and Sondergaard, HB and Sellebjerg, F and Sorensen, PS and Gomez, R and Caillier, SJ and Cree, BAC and Oksenberg, JR and Hauser, SL and D'Alfonso, S and Leone, MA and Martinelli Boneschi, F and Sorosina, M and van der Mei, I and Taylor, BV and Zhou, Y and Schaefer, C and Barcellos, LF, Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies, Neurology: Genetics, 2, (4) Article e87. ISSN 2376-7839 (2016) [Refereed Article]
Copyright 2016 American Academy of Neurology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/
METHODS: Ten unique MS case data sets were analyzed. The Multiple Sclerosis Severity Score (MSSS) was calculated using the Expanded Disability Status Scale at study entry and disease duration. MSSS was considered as a continuous variable and as 2 dichotomous variables (median and extreme ends; MSSS of ≤5 vs >5 and MSSS of <2.5 vs ≥7.5, respectively). Single nucleotide polymorphisms (SNPs) were examined individually and as both combined weighted genetic risk score (wGRS) and unweighted genetic risk score (GRS) for association with disease severity. Random-effects meta-analyses were conducted and adjusted for cohort, sex, age at onset, and HLA-DRB1*15:01.
RESULTS: A total of 7,125 MS cases were analyzed. The wGRS and GRS were not strongly associated with disease severity after accounting for cohort, sex, age at onset, and HLA-DRB1*15:01. After restricting analyses to cases with disease duration ≥10 years, associations were null (p value ≥0.05). No SNP was associated with disease severity after adjusting for multiple testing.
CONCLUSIONS: The largest meta-analysis of established MS genetic risk variants and disease severity, to date, was performed. Results suggest that the investigated MS genetic risk variants are not associated with MSSS, even after controlling for potential confounders. Further research in large cohorts is needed to identify genetic determinants of disease severity using sensitive clinical and MRI measures, which are critical to understanding disease mechanisms and guiding development of effective treatments.
|Item Type:||Refereed Article|
|Research Division:||Biomedical and Clinical Sciences|
|Research Field:||Central nervous system|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||van der Mei, I (Professor Ingrid van der Mei)|
|UTAS Author:||Taylor, BV (Professor Bruce Taylor)|
|UTAS Author:||Zhou, Y (Mr Yuan Zhou)|
|Deposited By:||Menzies Institute for Medical Research|
|Downloads:||176 View Download Statistics|
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