Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations

• 成果类型: Article
• 署名作者: Barrie, William; Yang, Yaoling; Irving-Pease, Evan K.; Attfield, Kathrine E.; Scorrano, Gabriele; Jensen, Lise Torp; Armen, Angelos P.; Dimopoulos, Evangelos Antonios; Stern, Aaron; Refoyo-Martinez, Alba; Pearson, Alice; Ramsoe, Abigail; Gaunitz, Charleen; Demeter, Fabrice; Jorkov, Marie Louise S.; Moller, Stig Bermann; Springborg, Bente; Klassen, Lutz; Hyldgard, Inger Marie; Wickmann, Niels; Vinner, Lasse; Korneliussen, Thorfinn Sand; Allentoft, Morten E.; Sikora, Martin; Kristiansen, Kristian; Rodriguez, Santiago; Nielsen, Rasmus; Iversen, Astrid K. N.; Lawson, Daniel J.; Fugger, Lars; Willerslev, Eske
• 署名单位: University of Cambridge; University of Bristol; University of Bristol; University of Copenhagen; University of Oxford; Aarhus University; University of Cambridge; University of California System; University of California Berkeley; University of Cambridge; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); Museum National d'Histoire Naturelle (MNHN); University of Copenhagen; Curtin University; University of Gothenburg; University of Oxford; University of Oxford; University of Bremen; University of Bremen
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6532
• DOI: 10.1038/s41586-023-06618-z
• 发表日期: 2024-01-11
• 页码: 321-328
• 关键词: rheumatoid-arthritis; association; admixture; selection; migration; genomics; insights; traits; reveal; atlas

摘要

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.