Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations

William Barrie, Yaoling Yang, Evan K. Irving-Pease, Kathrine E. Attfield, Gabriele Scorrano, Lise Torp Jensen, Angelos P. Armen, Evangelos Antonios Dimopoulos, Aaron Stern, Alba Refoyo-Martinez, Alice Pearson, Abigail Ramsøe, Charleen Gaunitz, Fabrice Demeter, Marie Louise S. Jørkov, Stig Bermann Møller, Bente Springborg, Lutz Klassen, Inger Marie Hyldgård, Niels Wickmann, Lasse Vinner, Thorfinn Sand Korneliussen, Morten E. Allentoft, Martin Sikora, Kristian Kristiansen, Santiago Rodriguez, Rasmus Nielsen, Astrid K. N. Iversen (), Daniel J. Lawson (), Lars Fugger () and Eske Willerslev ()
Additional contact information
William Barrie: University of Cambridge
Yaoling Yang: University of Bristol
Evan K. Irving-Pease: University of Copenhagen
Kathrine E. Attfield: University of Oxford
Gabriele Scorrano: University of Copenhagen
Lise Torp Jensen: University of Oxford
Angelos P. Armen: University of Oxford
Evangelos Antonios Dimopoulos: University of Cambridge
Aaron Stern: University of California, Berkeley
Alba Refoyo-Martinez: University of Copenhagen
Alice Pearson: University of Cambridge
Abigail Ramsøe: University of Copenhagen
Charleen Gaunitz: University of Copenhagen
Fabrice Demeter: University of Copenhagen
Marie Louise S. Jørkov: University of Copenhagen
Stig Bermann Møller: Ålborg Historiske Museum, Nordjyske Museer
Bente Springborg: Ålborg Historiske Museum, Nordjyske Museer
Lutz Klassen: Museum Østdanmark–Djursland og Randers
Inger Marie Hyldgård: Museum Østdanmark–Djursland og Randers
Niels Wickmann: Museum Vestsjælland
Lasse Vinner: University of Copenhagen
Thorfinn Sand Korneliussen: University of Copenhagen
Morten E. Allentoft: University of Copenhagen
Martin Sikora: University of Copenhagen
Kristian Kristiansen: University of Copenhagen
Santiago Rodriguez: University of Bristol
Rasmus Nielsen: University of Copenhagen
Astrid K. N. Iversen: University of Oxford
Daniel J. Lawson: University of Bristol
Lars Fugger: University of Oxford
Eske Willerslev: University of Cambridge

Nature, 2024, vol. 625, issue 7994, 321-328

Abstract: 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 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.

Date: 2024
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DOI: 10.1038/s41586-023-06618-z

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