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, Katharine Harding, Rod Middleton, Tarunya Arun, Waqar Rashid, Adil Harroud, Huw R Morris, Eli Silber, Gavin Giovannoni, Alastair J Noyce, Ruth Dobson
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.
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.