RT Journal Article
SR Electronic
T1 Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams & Wilkins
SP e87
DO 10.1212/NXG.0000000000000087
VO 2
IS 4
A1 Michaela F. George
A1 Farren B.S. Briggs
A1 Xiaorong Shao
A1 Milena A. Gianfrancesco
A1 Ingrid Kockum
A1 Hanne F. Harbo
A1 Elisabeth G. Celius
A1 Steffan D. Bos
A1 Anna Hedström
A1 Ling Shen
A1 Allan Bernstein
A1 Lars Alfredsson
A1 Jan Hillert
A1 Tomas Olsson
A1 Nikolaos A. Patsopoulos
A1 Philip L. De Jager
A1 Annette B. Oturai
A1 Helle B. Søndergaard
A1 Finn Sellebjerg
A1 Per S. Sorensen
A1 Refujia Gomez
A1 Stacy J. Caillier
A1 Bruce A.C. Cree
A1 Jorge R. Oksenberg
A1 Stephen L. Hauser
A1 Sandra D'Alfonso
A1 Maurizio A. Leone
A1 Filippo Martinelli Boneschi
A1 Melissa Sorosina
A1 Ingrid van der Mei
A1 Bruce V. Taylor
A1 Yuan Zhou
A1 Catherine Schaefer
A1 Lisa F. Barcellos
YR 2016
UL http://ng.neurology.org/content/2/4/e87.abstract
AB 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.CI=confidence interval; EAE=experimental autoimmune encephalomyelitis; EDSS=Expanded Disability Severity Scale; GRS=unweighted genetic risk score; GWAS=genome-wide association studies; KPNC=Kaiser Permanente Medical Care Plan in the Northern California Region; MHC=major histocompatibility complex; MS=multiple sclerosis; MSSS=Multiple Sclerosis Severity Score; OR=odds ratio; SNP=single nucleotide polymorphism; UCSF=University of California at San Francisco; wGRS=weighted genetic risk score