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Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies

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posted on 2023-05-18, 21:47 authored by George, MF, Briggs, FBS, Shao, X, Gianfrancesco, MA, Kockum, I, Harbo, HF, Celius, EG, Bos, SD, Hedstrom, A, Shen, L, Bernstein, A, Alfredsson, L, Hillert, J, Olsson, T, Patsopoulos, NA, De Jager, PL, Oturai, AB, Sondergaard, HB, Sellebjerg, F, Sorensen, PS, Gomez, R, Caillier, SJ, Cree, BAC, Oksenberg, JR, Hauser, SL, D'Alfonso, S, Leone, MA, Martinelli Boneschi, F, Sorosina, M, Ingrid van der MeiIngrid van der Mei, Bruce TaylorBruce Taylor, Yuan ZhouYuan Zhou, Schaefer, C, Barcellos, LF
OBJECTIVE: We investigated the association between 52 risk variants identified through genome-wide association studies and disease severity in multiple sclerosis (MS).

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.

History

Publication title

Neurology: Genetics

Issue

4

Article number

e87

Number

e87

Pagination

1-11

ISSN

2376-7839

Department/School

Menzies Institute for Medical Research

Publisher

Wolters Kluwer Health

Place of publication

United States

Rights statement

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/

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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