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

Michaela George; Farren B. S. Briggs; Xiaorong Shao; Milena A. Gianfrancesco; Ingrid Kockum; Hanne F. Harbo; Elisabeth G. Celius; Steffan D. Bos; Anna Hedström; Ling Shen; Allan Bernstein; Lars Alfredsson; Jan Hillert; Tomas Olsson; Nikolaos A. Patsopoulos; Philip L. De Jager; Annette B. Oturai; Helle B. Søndergaard; Finn Sellebjerg; Per S. Sorensen; Refujia Gomez; Stacy J. Caillier; Bruce A. C. Cree; Jorge R. Oksenberg; Stephen L. Hauser; Sandra D'Alfonso; Maurizio A. Leone; Filippo Martinelli Boneschi; Melissa Sorosina; Ingrid van der Mei; Bruce V. Taylor; Yuan Zhou; Catherine Schaefer; Lisa F. Barcellos

doi:10.1212/NXG.0000000000000087

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

Michaela George, Farren B. S. Briggs, Xiaorong Shao, Milena A. Gianfrancesco, Ingrid Kockum, Hanne F. Harbo, Elisabeth G. Celius, Steffan D. Bos, Anna Hedström, Ling Shen, Allan Bernstein, Lars Alfredsson, Jan Hillert, Tomas Olsson, Nikolaos A. Patsopoulos, Philip L. De Jager, Annette B. Oturai, Helle B. Søndergaard, Finn Sellebjerg, Per S. SorensenRefujia Gomez, Stacy J. Caillier, Bruce A. C. Cree, Jorge R. Oksenberg, Stephen L. Hauser, Sandra D'Alfonso, Maurizio A. Leone, Filippo Martinelli Boneschi, Melissa Sorosina, Ingrid van der Mei, Bruce V. Taylor, Yuan Zhou, Catherine Schaefer, Lisa F. Barcellos

Department of Global Public Health

Research output: Contribution to journal › Article › peer-review

Abstract

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

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.

Original language	American English
Journal	Neurology Genetics
Volume	2
Issue number	4
DOIs	https://doi.org/10.1212/NXG.0000000000000087
State	Published - 2016

Funding

This work was supported by the NIH/National Institute of Neurological Disorders and Stroke R01NS049510, NIH/National Institute of Allergy and Infectious Diseases R01AI076544, and NIH/National Institute of Environmental Health Sciences R01 ES017080; Foundation for Multiple Sclerosis (grants “Progetto Speciale Immunochip,” 2011/R/14, Fondazione cariplo [2010-0728]); and NIH/National Institute of Neurological Disorders and Stroke R01NS026799 and NIH/National Institute of Neurological Disorders and Stroke R01NS049477.

Disciplines

Public Health

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Multiple sclerosis risk loci and disease severity in 7125 indivi

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George, M., Briggs, F. B. S., Shao, X., Gianfrancesco, M. A., Kockum, I., Harbo, H. F., Celius, E. G., Bos, S. D., Hedström, A., Shen, L., Bernstein, A., Alfredsson, L., Hillert, J., Olsson, T., Patsopoulos, N. A., Jager, P. L. D., Oturai, A. B., Søndergaard, H. B., Sellebjerg, F., ... Barcellos, L. F. (2016). Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies. Neurology Genetics, 2(4). https://doi.org/10.1212/NXG.0000000000000087

George, M, Briggs, FBS, Shao, X, Gianfrancesco, MA, Kockum, I, Harbo, HF, Celius, EG, Bos, SD, Hedström, A, Shen, L, Bernstein, A, Alfredsson, L, Hillert, J, Olsson, T, Patsopoulos, NA, Jager, PLD, Oturai, AB, Søndergaard, HB, Sellebjerg, F, Sorensen, PS, Gomez, R, Caillier, SJ, Cree, BAC, Oksenberg, JR, Hauser, SL, D'Alfonso, S, Leone, MA, Boneschi, FM, Sorosina, M, van der Mei, I, Taylor, BV, Zhou, Y, Schaefer, C & Barcellos, LF 2016, 'Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies.', Neurology Genetics, vol. 2, no. 4. https://doi.org/10.1212/NXG.0000000000000087

@article{c24b9e3b7856491187426cfd8556c6c7,

title = "Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies.",

abstract = "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 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.",

author = "Michaela George and Briggs, {Farren B. S.} and Xiaorong Shao and Gianfrancesco, {Milena A.} and Ingrid Kockum and Harbo, {Hanne F.} and Celius, {Elisabeth G.} and Bos, {Steffan D.} and Anna Hedstr{\"o}m and Ling Shen and Allan Bernstein and Lars Alfredsson and Jan Hillert and Tomas Olsson and Patsopoulos, {Nikolaos A.} and Jager, {Philip L. De} and Oturai, {Annette B.} and S{\o}ndergaard, {Helle B.} and Finn Sellebjerg and Sorensen, {Per S.} and Refujia Gomez and Caillier, {Stacy J.} and Cree, {Bruce A. C.} and Oksenberg, {Jorge R.} and Hauser, {Stephen L.} and Sandra D'Alfonso and Leone, {Maurizio A.} and Boneschi, {Filippo Martinelli} and Melissa Sorosina and {van der Mei}, Ingrid and Taylor, {Bruce V.} and Yuan Zhou and Catherine Schaefer and Barcellos, {Lisa F.}",

year = "2016",

doi = "10.1212/NXG.0000000000000087",

language = "American English",

volume = "2",

journal = "Neurology Genetics",

number = "4",

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TY - JOUR

T1 - Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies.

AU - George, Michaela

AU - Briggs, Farren B. S.

AU - Shao, Xiaorong

AU - Gianfrancesco, Milena A.

AU - Kockum, Ingrid

AU - Harbo, Hanne F.

AU - Celius, Elisabeth G.

AU - Bos, Steffan D.

AU - Hedström, Anna

AU - Shen, Ling

AU - Bernstein, Allan

AU - Alfredsson, Lars

AU - Hillert, Jan

AU - Olsson, Tomas

AU - Patsopoulos, Nikolaos A.

AU - Jager, Philip L. De

AU - Oturai, Annette B.

AU - Søndergaard, Helle B.

AU - Sellebjerg, Finn

AU - Sorensen, Per S.

AU - Gomez, Refujia

AU - Caillier, Stacy J.

AU - Cree, Bruce A. C.

AU - Oksenberg, Jorge R.

AU - Hauser, Stephen L.

AU - D'Alfonso, Sandra

AU - Leone, Maurizio A.

AU - Boneschi, Filippo Martinelli

AU - Sorosina, Melissa

AU - van der Mei, Ingrid

AU - Taylor, Bruce V.

AU - Zhou, Yuan

AU - Schaefer, Catherine

AU - Barcellos, Lisa F.

PY - 2016

Y1 - 2016

N2 - 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 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.

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 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.

U2 - 10.1212/NXG.0000000000000087

DO - 10.1212/NXG.0000000000000087

M3 - Article

VL - 2

JO - Neurology Genetics

JF - Neurology Genetics

IS - 4

ER -