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; Eske Willerslev

doi:10.1038/s41586-023-06618-z

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 WickmannLasse Vinner, Thorfinn Sand Korneliussen, Morten E Allentoft, Martin Sikora, Kristian Kristiansen, Santiago Rodriguez, Rasmus Nielsen, Astrid K N Iversen^*, Daniel J Lawson^*, Lars Fugger^*, Eske Willerslev^*

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin - Immunologi

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

59 Citationer (Scopus)

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 1. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age 2, 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.

Originalsprog	Engelsk
Tidsskrift	Nature
Vol/bind	625
Sider (fra-til)	321-328
Antal sider	8
ISSN	0028-0836
DOI	https://doi.org/10.1038/s41586-023-06618-z
Status	Udgivet - jan. 2024

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Barrie, W., Yang, Y., Irving-Pease, E. K., Attfield, K. E., Scorrano, G., Jensen, L. T., Armen, A. P., Dimopoulos, E. A., Stern, A., Refoyo-Martinez, A., Pearson, A., Ramsøe, A., Gaunitz, C., Demeter, F., Jørkov, M. L. S., Møller, S. B., Springborg, B., Klassen, L., Hyldgård, I. M., ... Willerslev, E. (2024). Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations. Nature, 625, 321-328. https://doi.org/10.1038/s41586-023-06618-z

@article{f518866214754ca7b28c6906aa3527d4,

title = "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 1. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age 2, 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. ",

keywords = "Humans, Datasets as Topic, Diet/ethnology, Europe/ethnology, Genetic Predisposition to Disease/history, Genetics, Medical, Genome, Human, Grassland, History, 15th Century, History, Ancient, History, Medieval, Human Migration/history, Life Style/ethnology, Multiple Sclerosis/genetics, Neurodegenerative Diseases/genetics, Population Density",

author = "William Barrie and Yaoling Yang and Irving-Pease, {Evan K} and Attfield, {Kathrine E} and Gabriele Scorrano and Jensen, {Lise Torp} and Armen, {Angelos P} and Dimopoulos, {Evangelos Antonios} and Aaron Stern and Alba Refoyo-Martinez and Alice Pearson and Abigail Rams{\o}e and Charleen Gaunitz and Fabrice Demeter and J{\o}rkov, {Marie Louise S} and M{\o}ller, {Stig Bermann} and Bente Springborg and Lutz Klassen and Hyldg{\aa}rd, {Inger Marie} and Niels Wickmann and Lasse Vinner and Korneliussen, {Thorfinn Sand} and Allentoft, {Morten E} and Martin Sikora and Kristian Kristiansen and Santiago Rodriguez and Rasmus Nielsen and Iversen, {Astrid K N} and Lawson, {Daniel J} and Lars Fugger and Eske Willerslev",

note = "(s).",

year = "2024",

month = jan,

doi = "10.1038/s41586-023-06618-z",

language = "English",

volume = "625",

pages = "321--328",

journal = "Nature",

issn = "0028-0836",

publisher = "Springer Nature",

}

Barrie, W, Yang, Y, Irving-Pease, EK, Attfield, KE, Scorrano, G, Jensen, LT, Armen, AP, Dimopoulos, EA, Stern, A, Refoyo-Martinez, A, Pearson, A, Ramsøe, A, Gaunitz, C, Demeter, F, Jørkov, MLS, Møller, SB, Springborg, B, Klassen, L, Hyldgård, IM, Wickmann, N, Vinner, L, Korneliussen, TS, Allentoft, ME, Sikora, M, Kristiansen, K, Rodriguez, S, Nielsen, R, Iversen, AKN, Lawson, DJ, Fugger, L & Willerslev, E 2024, 'Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations', Nature, bind 625, s. 321-328. https://doi.org/10.1038/s41586-023-06618-z

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 - (s).

PY - 2024/1

Y1 - 2024/1

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 originated 1. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age 2, 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 originated 1. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age 2, 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.

KW - Humans

KW - Datasets as Topic

KW - Diet/ethnology

KW - Europe/ethnology

KW - Genetic Predisposition to Disease/history

KW - Genetics, Medical

KW - Genome, Human

KW - Grassland

KW - History, 15th Century

KW - History, Ancient

KW - History, Medieval

KW - Human Migration/history

KW - Life Style/ethnology

KW - Multiple Sclerosis/genetics

KW - Neurodegenerative Diseases/genetics

KW - Population Density

U2 - 10.1038/s41586-023-06618-z

DO - 10.1038/s41586-023-06618-z

M3 - Journal article

C2 - 38200296

SN - 0028-0836

VL - 625

SP - 321

EP - 328

JO - Nature

JF - Nature

ER -

Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations

Abstract

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