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Journal article

Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations

Abstract:
Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that is most prevalent in Northern Europe. Although it is known that inherited risk for MS is located within or in close proximity to immune-related genes, it is unknown when, where and how this genetic risk originated. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age, along with new Medieval and post-Medieval genomes, we show that the genetic risk for MS rose among pastoralists from the Pontic steppe and was brought into Europe by the Yamnaya-related migration approximately 5,000 years ago. We further show that these MS-associated immunogenetic variants underwent positive selection both within the steppe population and later in Europe, probably driven by pathogenic challenges coinciding with changes in diet, lifestyle and population density. This study highlights the critical importance of the Neolithic period and Bronze Age as determinants of modern immune responses and their subsequent effect on the risk of developing MS in a changing environment.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41586-023-06618-z

Authors

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Role:
Author
ORCID:
0000-0003-4905-8097
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Role:
Author
ORCID:
0000-0003-1940-2192
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Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
ORCID:
0000-0003-3387-521X
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Role:
Author
ORCID:
0000-0002-0887-4023


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Funder identifier:
https://ror.org/029chgv08
Grant:
214300


Publisher:
Nature Research
Journal:
Nature More from this journal
Volume:
625
Issue:
7994
Pages:
321-328
Publication date:
2024-01-10
Acceptance date:
2023-09-06
DOI:
EISSN:
1476-4687
ISSN:
0028-0836
Pmid:
38200296


Language:
English
Keywords:
Pubs id:
1601457
Local pid:
pubs:1601457
Source identifiers:
W4390705788
Deposit date:
2024-07-10
ARK identifier:

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