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Elevated genetic ri...
Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations
- Article/chapterEnglish2024
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LIBRIS-ID:oai:gup.ub.gu.se/335282
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https://gup.ub.gu.se/publication/335282URI
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https://doi.org/10.1038/s41586-023-06618-zDOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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 originated1. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age2, 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. Analysis of a large ancient genome dataset shows that genetic risk for multiple sclerosis rose in steppe pastoralists, providing insight into how genetic ancestry from the Neolithic and Bronze Age has shaped modern immune responses.
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Yang, Yaoling
(author)
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Irving-Pease, Evan K.
(author)
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Attfield, Kathrine E.
(author)
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Scorrano, Gabriele
(author)
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Jensen, Lise Torp
(author)
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Armen, Angelos P.
(author)
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Dimopoulos, Evangelos Antonios
(author)
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Stern, Aaron
(author)
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Refoyo-Martinez, Alba
(author)
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Pearson, Alice
(author)
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Ramsoe, Abigail
(author)
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Gaunitz, Charleen
(author)
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Demeter, Fabrice
(author)
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Jorkov, Marie Louise S.
(author)
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Moller, Stig Bermann
(author)
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Springborg, Bente
(author)
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Klassen, Lutz
(author)
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Hyldgard, Inger Marie
(author)
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Wickmann, Niels
(author)
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Vinner, Lasse
(author)
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Korneliussen, Thorfinn Sand
(author)
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Allentoft, Morten E.
(author)
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Sikora, Martin
(author)
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Kristiansen, Kristian,1948Gothenburg University,Göteborgs universitet,Institutionen för historiska studier,Department of Historical Studies(Swepub:gu)xkrikr
(author)
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Rodriguez, Santiago
(author)
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Nielsen, Rasmus
(author)
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Iversen, Astrid K. N.
(author)
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Lawson, Daniel J.
(author)
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Fugger, Lars
(author)
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Willerslev, Eske
(author)
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Göteborgs universitetInstitutionen för historiska studier
(creator_code:org_t)
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In:NATURE625:79940028-08361476-4687
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Yang, Yaoling
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Armen, Angelos P ...
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Dimopoulos, Evan ...
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Pearson, Alice
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Ramsoe, Abigail
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Gaunitz, Charlee ...
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Demeter, Fabrice
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Jorkov, Marie Lo ...
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Moller, Stig Ber ...
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Springborg, Bent ...
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Klassen, Lutz
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Hyldgard, Inger ...
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Wickmann, Niels
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Vinner, Lasse
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Korneliussen, Th ...
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Allentoft, Morte ...
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Sikora, Martin
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Kristiansen, Kri ...
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Rodriguez, Santi ...
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Nielsen, Rasmus
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