Association Between Genetic Ancestry and Multiple Sclerosis Severity
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.
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Authors: Benjamin M. Jacobs, Emily Tregaskis-Daniels, Luisa Schalk, Jakub Nagrodski, ADAMS investigators, Michelle Peter, Rashmi Kaimal, Roxanne Murray, Sadid Hoque, Terri‐Louise Brown, Ghaniah Hassan-Smith, Helen L. Ford, Bruno Gran, Karim L. Kreft, Cord Spilker, Outi Quinn, David Rog, Miriam Mattoscio, Elisa Visentin, Ramya Shamji, Grace Fawehinmi, Katila George, Maria Papachatzaki, Harding Katharine, Rod Middleton, Tarunya Arun, Waqar Rashid, Adil Harroud, Huw R. Morris, Eli Silber, Gavin Giovannoni, Alastair John Noyce, Ruth Dobson
Institutions: Nottingham University Hospitals NHS Trust, University College London, McGill University, Queen Mary University of London, Swansea University, National Hospital for Neurology and Neurosurgery, Leeds Teaching Hospitals NHS Trust, Lewisham and Greenwich NHS Trust, King's College Hospital NHS Foundation Trust, Barking, Havering And Redbridge University Hospitals NHS Trust, Montreal Neurological Institute and Hospital, Barts Health NHS Trust, Royal London Hospital, University Hospitals Birmingham NHS Foundation Trust, University Hospital Coventry, University Hospitals Coventry and Warwickshire NHS Trust, St George’s University Hospitals NHS Foundation Trust, Bradford Teaching Hospitals NHS Foundation Trust, Aneurin Bevan University Health Board, UCL Queen Square Institute of Neurology