Genetic risk for Multiple Sclerosis originated in Pastoralist Steppe populations
Publikation: Working paper › Preprint › Forskning
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Genetic risk for Multiple Sclerosis originated in Pastoralist Steppe populations. / Barrie, William; Yang, Yaoling; Attfield, Kathrine E.; Irving-Pease, Evan; Scorrano, Gabriele; Jensen, Lise Torp; Armen, Angelos P.; Dimopoulos, Evangelos Antonios; Stern, Aaron; Refoyo-Martínez, Alba; Ramsøe, Abigail; Gaunitz, Charleen; Demeter, Fabrice; Jørkov, Marie Louise S.; Møller, Stig Bermann; Springborg, Bente; Klassen, Lutz; Hyldgård, Inger Marie; Wickmann, Niels; Vinner, Lasse; Korneliussen, Thorfinn Sand; Sikora, Martin; Kristiansen, Kristian; Rodriguez, Santiago; Nielsen, Rasmus; Iversen, Astrid K. N.; Lawson, Daniel J.; Fugger, Lars; Willerslev, Eske.
bioRxiv, 2022.Publikation: Working paper › Preprint › Forskning
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TY - UNPB
T1 - Genetic risk for Multiple Sclerosis originated in Pastoralist Steppe populations
AU - Barrie, William
AU - Yang, Yaoling
AU - Attfield, Kathrine E.
AU - Irving-Pease, Evan
AU - Scorrano, Gabriele
AU - Jensen, Lise Torp
AU - Armen, Angelos P.
AU - Dimopoulos, Evangelos Antonios
AU - Stern, Aaron
AU - Refoyo-Martínez, Alba
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 - 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
PY - 2022
Y1 - 2022
N2 - Multiple sclerosis (MS) is a modern neuro-inflammatory and -degenerative disease, which is most prevalent in Northern Europe. Whilst it is known that inherited risk to MS is located within or within close proximity to immune genes it is unknown when, where and how this genetic risk originated. By using the largest ancient genome dataset from the Stone Age, along with new Medieval and post-Medieval genomes, we show that many of the genetic risk variants for MS rose to higher frequency among pastoralists located on the Pontic Steppe, and were 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, likely driven by pathogenic challenges coinciding with dietary and lifestyle environmental changes. This study highlights the critical importance of this period as a determinant of modern immune responses and its subsequent impact on the risk of developing MS in a changing environment.
AB - Multiple sclerosis (MS) is a modern neuro-inflammatory and -degenerative disease, which is most prevalent in Northern Europe. Whilst it is known that inherited risk to MS is located within or within close proximity to immune genes it is unknown when, where and how this genetic risk originated. By using the largest ancient genome dataset from the Stone Age, along with new Medieval and post-Medieval genomes, we show that many of the genetic risk variants for MS rose to higher frequency among pastoralists located on the Pontic Steppe, and were 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, likely driven by pathogenic challenges coinciding with dietary and lifestyle environmental changes. This study highlights the critical importance of this period as a determinant of modern immune responses and its subsequent impact on the risk of developing MS in a changing environment.
U2 - 10.1101/2022.09.23.509097
DO - 10.1101/2022.09.23.509097
M3 - Preprint
BT - Genetic risk for Multiple Sclerosis originated in Pastoralist Steppe populations
PB - bioRxiv
ER -
ID: 327687466