Association Between Genetic Ancestry and Multiple Sclerosis Severity

OBJECTIVE: The objective of this study was to determine whether genetic ancestry is associated with differences in the clinical course of multiple sclerosis (MS). METHODS: Participants with MS living in the United Kingdom >18 years old were recruited from 2021 to 2025 and genotyped from saliva using a commercial array. Genetic ancestry was inferred using a random forest classifier trained on a diverse reference dataset. Participant-reported MS characteristics including the Age-Related Multiple Sclerosis Severity Score (ARMSS) and age at MS diagnosis were ascertained at recruitment. RESULTS: We analyzed data from 816 people with MS (pwMS), comprising 260 people of South Asian ancestry (31.9%), 163 of African ancestry (20.0%), 316 of European ancestry (38.7%), and 77 participants from other backgrounds. The included cohort was predominantly female (72.3% women), diagnosed with MS at a median age of 32 years (interquartile range [IQR] = 14.0) and recruited at a median age of 44.6 years (IQR = 18.2). Neither South Asian nor African ancestry was consistently associated with higher MS severity compared with European-ancestry participants. No genetic variants were associated with MS severity at genomewide statistical significance. INTERPRETATION: In this cross-sectional, diverse, UK cohort, neither South Asian nor African ancestry is associated with greater MS-related disability. These findings argue against a genetic basis for the previously observed differences between MS outcomes when contrasting ethnic groups. ANN NEUROL 2026.

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Publication Details

Journal
Annals of Neurology
Published
2026-09-25
DOI
https://doi.org/10.1002/ana.78350
Primary Topic
Multiple Sclerosis Research Studies
Type
article
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article

Association Between Genetic Ancestry and Multiple Sclerosis Severity

Benjamin M. Jacobs, Ruth Dobson, Outi Quinn, Cord Spilker et al.
Annals of Neurology
Multiple Sclerosis Research Studies
article

Association Between Genetic Ancestry and Multiple Sclerosis Severity

Benjamin M. Jacobs, Ruth Dobson, Outi Quinn, Cord Spilker, Waqar Rashid, Maria Papachatzaki, Alastair John Noyce, Tarunya Arun, Adil Harroud, Huw R. Morris, Miriam Mattoscio, Luisa Schalk, Ramya Shamji, Rashmi Kaimal, Harding Katharine, Emily Tregaskis-Daniels, Roxanne Murray, Grace Fawehinmi, Ghaniah Hassan-Smith, David Rog, Rod Middleton, Sadid Hoque, Bruno Gran, Katila George, Terri‐Louise Brown, Elisa Visentin, Gavin Giovannoni, Eli Silber, ADAMS investigators, Jakub Nagrodski, Helen L. Ford, Karim L. Kreft, Michelle Peter
article en

Abstract

OBJECTIVE: The objective of this study was to determine whether genetic ancestry is associated with differences in the clinical course of multiple sclerosis (MS). METHODS: Participants with MS living in the United Kingdom >18 years old were recruited from 2021 to 2025 and genotyped from saliva using a commercial array. Genetic ancestry was inferred using a random forest classifier trained on a diverse reference dataset. Participant-reported MS characteristics including the Age-Related Multiple Sclerosis Severity Score (ARMSS) and age at MS diagnosis were ascertained at recruitment. RESULTS: We analyzed data from 816 people with MS (pwMS), comprising 260 people of South Asian ancestry (31.9%), 163 of African ancestry (20.0%), 316 of European ancestry (38.7%), and 77 participants from other backgrounds. The included cohort was predominantly female (72.3% women), diagnosed with MS at a median age of 32 years (interquartile range [IQR] = 14.0) and recruited at a median age of 44.6 years (IQR = 18.2). Neither South Asian nor African ancestry was consistently associated with higher MS severity compared with European-ancestry participants. No genetic variants were associated with MS severity at genomewide statistical significance. INTERPRETATION: In this cross-sectional, diverse, UK cohort, neither South Asian nor African ancestry is associated with greater MS-related disability. These findings argue against a genetic basis for the previously observed differences between MS outcomes when contrasting ethnic groups. ANN NEUROL 2026.

Annals of Neurology
Montreal Neurological Institute and Hospital (CA), Barking, Havering And Redbridge University Hospitals NHS Trust (GB), University Hospitals Birmingham NHS Foundation Trust (GB), Nottingham University Hospitals NHS Trust (GB), Queen Mary University of London (GB), Barts Health NHS Trust (GB), Leeds Teaching Hospitals NHS Trust (GB), St George’s University Hospitals NHS Foundation Trust (GB), Royal London Hospital (GB), University Hospital Coventry (GB), Aneurin Bevan University Health Board (GB), University Hospitals Coventry and Warwickshire NHS Trust (GB), Swansea University (GB), King's College Hospital NHS Foundation Trust (GB), National Hospital for Neurology and Neurosurgery (GB), Lewisham and Greenwich NHS Trust (GB), Bradford Teaching Hospitals NHS Foundation Trust (GB), UCL Queen Square Institute of Neurology (GB), University College London (GB), McGill University (CA)
Openalex Percentile: Top 12%
Multiple Sclerosis Research Studies
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