ArticlePLoS genetics2019
Admixture mapping reveals evidence of differential multiple sclerosis risk by genetic ancestry.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- The role of machine learning in developing non-magnetic resonance imaging based biomarkers for multiple sclerosis: a systematic review.BMC medical informatics and decision making · 2022Pooled it
- Two Years of Ocrelizumab Treatment in Black and Hispanic People with Multiple Sclerosis in CHIMES: A Single-Arm Clinical Trial.Annals of neurology · 2026Trial
- Efficacy of Ofatumumab and Teriflunomide in Patients With Relapsing MS From Racial/Ethnic Minority Groups: ASCLEPIOS I/II Subgroup Analyses.Neurology · 2024Trial
- Admixture mapping identifies complex trait associations with local ancestry in themedRxiv : the preprint server for health sciences · 2025Article
- Differential results of genetic risk scoring for multiple sclerosis in European and African American populations.Multiple sclerosis (Houndmills, Basingstoke, England) · 2025Article
- Incorporating local ancestry information to predict genetically associated DNA methylation in admixed populations.Briefings in bioinformatics · 2025Observational
- Embodiment of structural racism and multiple sclerosis risk and outcomes in the USA.Nature reviews. Neurology · 2025Review
- Across ancestries, HLA-B∗08:01∼DRB1∗03:01 (DR3) and HLA-DQA∗01:02 (DR2) increase the risk to develop juvenile-onset systemic lupus erythematosus through low complement C4 levels.Journal of translational autoimmunity · 2025Article
- Racial and Ethnic Disease Phenotype Differences Are Driven by Genetics: Commentary.Multiple sclerosis (Houndmills, Basingstoke, England) · 2024Article
- Prevalence of neuromyelitis optica spectrum disorder in the United States.Multiple sclerosis (Houndmills, Basingstoke, England) · 2024Article
- Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations.Nature · 2024Article
- Principles and methods for transferring polygenic risk scores across global populations.Nature reviews. Genetics · 2024Review
- Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape.Nature communications · 2023Review
- Juvenile multiple sclerosis: addressing epidemiology, diagnosis, therapeutic, and prognostic updates along with cognitive dysfunction and quality of life.Annals of medicine and surgery (2012) · 2023Review
- ADAMS project: a genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis based in the UK.BMJ open · 2023Article
- Health Disparities in Multiple Sclerosis among Hispanic and Black Populations in the United States.Biomedicines · 2023Review
- Whole-Exome Sequencing in Family Trios Reveals De Novo Mutations Associated with Type 1 Diabetes Mellitus.Biology · 2023Article
- Do magnetic resonance imaging features differ between persons with multiple sclerosis of various races and ethnicities?Frontiers in neurology · 2023Review
- Consent Codes: Maintaining Consent in an Ever-expanding Open Science Ecosystem.Neuroinformatics · 2023Article
- Polygenic risk score prediction of multiple sclerosis in individuals of South Asian ancestry.Brain communications · 2023Article
Corrections and comments
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Authors and funding
33 authors at 19 institutions in 1 country.
Funding
Abstract
Multiple sclerosis (MS) is an autoimmune disease with high prevalence among populations of northern European ancestry. Past studies have shown that exposure to ultraviolet radiation could explain the difference in MS prevalence across the globe. In this study, we investigate whether the difference in MS prevalence could be explained by European genetic risk factors. We characterized the ancestry of MS-associated alleles using RFMix, a conditional random field parameterized by random forests, to estimate their local ancestry in the largest assembled admixed population to date, with 3,692 African Americans, 4,915 Asian Americans, and 3,777 Hispanics. The majority of MS-associated human leukocyte antigen (HLA) alleles, including the prominent HLA-DRB1*15:01 risk allele, exhibited cosmopolitan ancestry. Ancestry-specific MS-associated HLA alleles were also identified. Analysis of the HLA-DRB1*15:01 risk allele in African Americans revealed that alleles on the European haplotype conferred three times the disease risk compared to those on the African haplotype. Furthermore, we found evidence that the European and African HLA-DRB1*15:01 alleles exhibit single nucleotide polymorphism (SNP) differences in regions encoding the HLA-DRB1 antigen-binding heterodimer. Additional evidence for increased risk of MS conferred by the European haplotype were found for HLA-B*07:02 and HLA-A*03:01 in African Americans. Most of the 200 non-HLA MS SNPs previously established in European populations were not significantly associated with MS in admixed populations, nor were they ancestrally more European in cases compared to controls. Lastly, a genome-wide search of association between European ancestry and MS revealed a region of interest close to the ZNF596 gene on chromosome 8 in Hispanics; cases had a significantly higher proportion of European ancestry compared to controls. In conclusion, our study established that the genetic ancestry of MS-associated alleles is complex and implicated that difference in MS prevalence could be explained by the ancestry of MS-associated alleles.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.