Annals of neurology · 2026
Association Between Genetic Ancestry and Multiple Sclerosis Severity.
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Jacobs Benjamin M, Tregaskis-Daniels Emily, Schalk Luisa, Nagrodski Jakub, ADAMS investigators, Peter Michelle, Kaimal Rashmi, Murray Roxanne, Hoque Sadid, Brown Terri-Louise, Hassan-Smith Ghaniah, Ford Helen L, Gran Bruno, Kreft Karim L, Spilker Cord, Quinn Outi, Rog David, Mattoscio Miriam, Visentin Elisa, Shamji Ramya, Fawehinmi Grace, George Katila, Papachatzaki Maria, Harding Katharine, Middleton Rod, Arun Tarunya, Rashid Waqar, Harroud Adil, Morris Huw R, Silber Eli, Giovannoni Gavin, Noyce Alastair J, Dobson Ruth
Аннотация
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.
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.