TY - JOUR
T1 - Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations
AU - Barrie, William
AU - Yang, Yaoling
AU - Irving-Pease, Evan K.
AU - Attfield, Kathrine E.
AU - Scorrano, Gabriele
AU - Jensen, Lise Torp
AU - Armen, Angelos P.
AU - Dimopoulos, Evangelos Antonios
AU - Stern, Aaron
AU - Refoyo-Martinez, Alba
AU - Pearson, Alice
AU - Ramsøe, Abigail
AU - Gaunitz, Charleen
AU - Demeter, Fabrice
AU - Jørkov, Marie Louise S.
AU - Møller, Stig Bermann
AU - Springborg, Bente
AU - Klassen, Lutz
AU - Hyldgård, Inger Marie
AU - Wickmann, Niels
AU - Vinner, Lasse
AU - Korneliussen, Thorfinn Sand
AU - Allentoft, Morten E.
AU - Sikora, Martin
AU - Kristiansen, Kristian
AU - Rodriguez, Santiago
AU - Nielsen, Rasmus
AU - Iversen, Astrid K. N.
AU - Lawson, Daniel J.
AU - Fugger, Lars
AU - Willerslev, Eske
N1 - Publisher Copyright:
© 2024, The Author(s).
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
U2 - 10.1038/s41586-023-06618-z
DO - 10.1038/s41586-023-06618-z
M3 - Journal article
C2 - 38200296
AN - SCOPUS:85181501928
VL - 625
SP - 321
EP - 328
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 7994
ER -