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  • Perspective
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Towards a global view of multiple sclerosis genetics

Abstract

Multiple sclerosis (MS) is a neuroimmunological disorder of the CNS with a strong heritable component. The genetic architecture of MS susceptibility is well understood in populations of European ancestry. However, the extent to which this architecture explains MS susceptibility in populations of non-European ancestry remains unclear. In this Perspective article, we outline the scientific arguments for studying MS genetics in ancestrally diverse populations. We argue that this approach is likely to yield insights that could benefit individuals with MS from all ancestral groups. We explore the logistical and theoretical challenges that have held back this field to date and conclude that, despite these challenges, inclusion of participants of non-European ancestry in MS genetics studies will ultimately be of value to all patients with MS worldwide.

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Fig. 1: Global variation in frequency of the HLA-DRB1*15:01 allele.
Fig. 2: Illustration of cross-ancestral fine mapping.

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Acknowledgements

The authors thank S. Sawcer, University of Cambridge, UK, for helpful comments on an early draft of the manuscript. B.M.J. is supported by an MRC Clinical Research Training Fellowship (grant reference MR/V028766/1).

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B.M.J. researched data for the article. B.M.J., G.G., A.J.N., H.R.M. and R.D. wrote the article. All authors made substantial contributions to discussion of the content and reviewed and edited the manuscript before submission.

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Correspondence to Benjamin Meir Jacobs.

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Nature Reviews Neurology thanks L. Amezcua; N. Isobe; J. McCauley, who co-reviewed with A. Beecham; M. Williams and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Jacobs, B.M., Peter, M., Giovannoni, G. et al. Towards a global view of multiple sclerosis genetics. Nat Rev Neurol 18, 613–623 (2022). https://doi.org/10.1038/s41582-022-00704-y

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