Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations.

Autor: Barrie W; Department of Zoology, University of Cambridge, Cambridge, UK.; Department of Genetics, University of Cambridge, Cambridge, UK., Yang Y; Department of Statistical Sciences, School of Mathematics, University of Bristol, Bristol, UK.; MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, UK., Irving-Pease EK; Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark., Attfield KE; Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK., Scorrano G; Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark., Jensen LT; Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.; Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark., Armen AP; Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK., Dimopoulos EA; Pathogen Genomics and Evolution Group, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK., Stern A; Departments of Integrative Biology and Statistics, University of California, Berkeley, Berkeley, CA, USA., Refoyo-Martinez A; Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark., Pearson A; Department of Genetics, University of Cambridge, Cambridge, UK., Ramsøe A; Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark., Gaunitz C; Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark., Demeter F; Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.; Eco-anthropologie (EA), Muséum National d'Histoire Naturelle, CNRS, Université de Paris, Musée de l'Homme, Paris, France., Jørkov MLS; Laboratory of Biological Anthropology, Department of Forensic Medicine, University of Copenhagen, Copenhagen, Denmark., Møller SB; Ålborg Historiske Museum, Nordjyske Museer, Vestbjerg, Denmark., Springborg B; Ålborg Historiske Museum, Nordjyske Museer, Vestbjerg, Denmark., Klassen L; Museum Østdanmark-Djursland og Randers, Randers, Denmark., Hyldgård IM; Museum Østdanmark-Djursland og Randers, Randers, Denmark., Wickmann N; Museum Vestsjælland, Holbæk, Denmark., Vinner L; Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark., Korneliussen TS; Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark., Allentoft ME; Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.; Trace and Environmental DNA (TrEnD) Laboratory, School of Molecular and Life Sciences, Curtin University, Perth, Western Australia, Australia., Sikora M; Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark., Kristiansen K; Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.; Department of Historical Studies, University of Gothenburg, Gothenburg, Sweden., Rodriguez S; MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, UK., Nielsen R; Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.; Departments of Integrative Biology and Statistics, University of California, Berkeley, Berkeley, CA, USA., Iversen AKN; Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK. astrid.iversen@ndcn.ox.ac.uk.; Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK. astrid.iversen@ndcn.ox.ac.uk., Lawson DJ; Department of Statistical Sciences, School of Mathematics, University of Bristol, Bristol, UK. dan.lawson@bristol.ac.uk.; MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, UK. dan.lawson@bristol.ac.uk., Fugger L; Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK. lars.fugger@ndcn.ox.ac.uk.; Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark. lars.fugger@ndcn.ox.ac.uk.; MRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK. lars.fugger@ndcn.ox.ac.uk., Willerslev E; Department of Zoology, University of Cambridge, Cambridge, UK. ew482@cam.ac.uk.; Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark. ew482@cam.ac.uk.; MARUM Center for Marine Environmental Sciences and Faculty of Geosciences, University of Bremen, Bremen, Germany. ew482@cam.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Jan; Vol. 625 (7994), pp. 321-328. Date of Electronic Publication: 2024 Jan 10.
DOI: 10.1038/s41586-023-06618-z
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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