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


Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
Jan 2024
Historique:
received: 21 09 2022
accepted: 06 09 2023
medline: 11 1 2024
pubmed: 11 1 2024
entrez: 10 1 2024
Statut: ppublish

Résumé

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

Identifiants

pubmed: 38200296
doi: 10.1038/s41586-023-06618-z
pii: 10.1038/s41586-023-06618-z
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

321-328

Informations de copyright

© 2024. The Author(s).

Références

Attfield, K. E., Jensen, L. T., Kaufmann, M., Friese, M. A. & Fugger, L. The immunology of multiple sclerosis. Nat. Rev. Immunol. https://doi.org/10.1038/s41577-022-00718-z (2022).
Allentoft, M. E. et al. Population genomics of post-glacial western Eurasia. Nature https://doi.org/10.1038/s41586-023-06865-0 (2024).
Walton, C. et al. Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition. Mult. Scler. J. 26, 1816–1821 (2020).
doi: 10.1177/1352458520970841
International Multiple Sclerosis Genetics Consortium et al. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science 365, eaav7188 (2019).
pmcid: 7241648 doi: 10.1126/science.aav7188
Bjornevik, K. et al. Longitudinal analysis reveals high prevalence of Epstein–Barr virus associated with multiple sclerosis. Science 375, 296–301 (2022).
pubmed: 35025605 doi: 10.1126/science.abj8222
Lanz, T. V. et al. Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM. Nature 603, 321–327 (2022).
pubmed: 35073561 pmcid: 9382663 doi: 10.1038/s41586-022-04432-7
Olsson, T., Barcellos, L. F. & Alfredsson, L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat. Rev. Neurol. 13, 25–36 (2017).
pubmed: 27934854 doi: 10.1038/nrneurol.2016.187
Benton, M. L. et al. The influence of evolutionary history on human health and disease. Nat. Rev. Genet. 22, 269–283 (2021).
pubmed: 33408383 pmcid: 7787134 doi: 10.1038/s41576-020-00305-9
Chi, C. et al. Admixture mapping reveals evidence of differential multiple sclerosis risk by genetic ancestry. PLoS Genet. 15, e1007808 (2019).
pubmed: 30653506 pmcid: 6353231 doi: 10.1371/journal.pgen.1007808
Bycroft, C. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 562, 203–209 (2018).
pubmed: 30305743 pmcid: 6786975 doi: 10.1038/s41586-018-0579-z
Irving-Pease, E. K. et al. The selection landscape and genetic legacy of ancient Eurasians. Nature https://doi.org/10.1038/s41586-023-06705-1 (2024).
Itan, Y., Powell, A., Beaumont, M. A., Burger, J. & Thomas, M. G. The origins of lactase persistence in Europe. PLoS Comput. Biol. 5, e1000491 (2009).
pubmed: 19714206 pmcid: 2722739 doi: 10.1371/journal.pcbi.1000491
Fugger, L., Jensen, L. T. & Rossjohn, J. Challenges, progress, and prospects of developing therapies to treat autoimmune diseases. Cell 181, 63–80 (2020).
pubmed: 32243797 doi: 10.1016/j.cell.2020.03.007
Dehasque, M. et al. Inference of natural selection from ancient DNA. Evol. Lett. 4, 94–108 (2020).
pubmed: 32313686 pmcid: 7156104 doi: 10.1002/evl3.165
Efron, B. Better bootstrap confidence intervals. J. Am. Stat. Assoc. 82, 171–185 (1987).
doi: 10.1080/01621459.1987.10478410
Zaykin, D. V. et al. Testing association of statistically inferred haplotypes with discrete and continuous traits in samples of unrelated individuals. Hum. Hered. 53, 79–91 (2002).
pubmed: 12037407 doi: 10.1159/000057986
Yang, Y. & Lawson, D. J. HTRX: an R package for learning non-contiguous haplotypes associated with a phenotype. Bioinform. Adv. 3, vbad038 (2023).
pubmed: 37033465 pmcid: 10074024 doi: 10.1093/bioadv/vbad038
Thuesen, N. H., Klausen, M. S., Gopalakrishnan, S., Trolle, T. & Renaud, G. Benchmarking freely available HLA typing algorithms across varying genes, coverages and typing resolutions. Frontiers Immunol. https://www.frontiersin.org/articles/10.3389/fimmu.2022.987655 (2022).
Stern, A. J., Wilton, P. R. & Nielsen, R. An approximate full-likelihood method for inferring selection and allele frequency trajectories from DNA sequence data. PLoS Genet. 15, e1008384 (2019).
pubmed: 31518343 pmcid: 6760815 doi: 10.1371/journal.pgen.1008384
Stern, A. J., Speidel, L., Zaitlen, N. A. & Nielsen, R. Disentangling selection on genetically correlated polygenic traits via whole-genome genealogies. Am. J. Hum. Genet. 108, 219–239 (2021).
pubmed: 33440170 pmcid: 7895848 doi: 10.1016/j.ajhg.2020.12.005
Jones, E. R. et al. Upper Palaeolithic genomes reveal deep roots of modern Eurasians. Nat. Commun. 6, 8912 (2015).
pubmed: 26567969 doi: 10.1038/ncomms9912
Comabella, M. et al. Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms. PLoS ONE 3, e3490 (2008).
pubmed: 18941528 pmcid: 2566815 doi: 10.1371/journal.pone.0003490
Bersaglieri, T. et al. Genetic signatures of strong recent positive selection at the lactase gene. Am. J. Hum. Genet. 74, 1111–1120 (2004).
pubmed: 15114531 pmcid: 1182075 doi: 10.1086/421051
He, Z., Dai, X., Beaumont, M. & Yu, F. Detecting and quantifying natural selection at two linked loci from time series data of allele frequencies with forward-in-time simulations. Genetics 216, 521–541 (2020).
pubmed: 32826299 pmcid: 7536848 doi: 10.1534/genetics.120.303463
Kurki, M. I. et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature 613, 508–518 (2023).
pubmed: 36653562 pmcid: 9849126 doi: 10.1038/s41586-022-05473-8
Haak, W. et al. Massive migration from the steppe was a source for Indo-European languages in Europe. Nature 522, 207–211 (2015).
pubmed: 25731166 pmcid: 5048219 doi: 10.1038/nature14317
Allentoft, M. E. et al. Population genomics of Bronze Age Eurasia. Nature 522, 167–172 (2015).
pubmed: 26062507 doi: 10.1038/nature14507
Gregersen, J. W. et al. Functional epistasis on a common MHC haplotype associated with multiple sclerosis. Nature 443, 574–577 (2006).
pubmed: 17006452 doi: 10.1038/nature05133
Wang, J. H. et al. Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data. Genome Med. 3, 3 (2011).
pubmed: 21244703 pmcid: 3092088 doi: 10.1186/gm217
Cotsapas, C. & Mitrovic, M. Genome-wide association studies of multiple sclerosis. Clin. Transl. Immunol. 7, e1018 (2018).
doi: 10.1002/cti2.1018
Slim, L., Chatelain, C., de Foucauld, H. & Azencott, C.-A. A systematic analysis of gene–gene interaction in multiple sclerosis. BMC Med. Genomics 15, 100 (2022).
pubmed: 35501860 pmcid: 9063218 doi: 10.1186/s12920-022-01247-3
Kerner, G. et al. Human ancient DNA analyses reveal the high burden of tuberculosis in Europeans over the last 2,000 years. Am. J. Hum. Genet. 108, 517–524 (2021).
pubmed: 33667394 pmcid: 8008489 doi: 10.1016/j.ajhg.2021.02.009
Kerner, G. et al. Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe. Cell Genomics 3, 100248 (2023).
pubmed: 36819665 pmcid: 9932995 doi: 10.1016/j.xgen.2022.100248
Bos, K. I. et al. Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis. Nature 514, 494–497 (2014).
pubmed: 25141181 pmcid: 4550673 doi: 10.1038/nature13591
Sabin, S. et al. A seventeenth-century Mycobacterium tuberculosis genome supports a Neolithic emergence of the Mycobacterium tuberculosis complex. Genome Biol. 21, 201 (2020).
pubmed: 32778135 pmcid: 7418204 doi: 10.1186/s13059-020-02112-1
Rasmussen, S. et al. Early divergent strains of Yersinia pestis in Eurasia 5,000 years ago. Cell 163, 571–582 (2015).
pubmed: 26496604 pmcid: 4644222 doi: 10.1016/j.cell.2015.10.009
Spyrou, M. A. et al. Analysis of 3800-year-old Yersinia pestis genomes suggests Bronze Age origin for bubonic plague. Nat. Commun. 9, 2234 (2018).
pubmed: 29884871 pmcid: 5993720 doi: 10.1038/s41467-018-04550-9
Rascovan, N. et al. Emergence and spread of basal lineages of Yersinia pestis during the Neolithic decline. Cell 176, 295–305 (2019).
pubmed: 30528431 doi: 10.1016/j.cell.2018.11.005
Düx, A. et al. Measles virus and rinderpest virus divergence dated to the sixth century BCE. Science 368, 1367–1370 (2020).
pubmed: 32554594 pmcid: 7713999 doi: 10.1126/science.aba9411
Guellil, M. et al. Ancient herpes simplex 1 genomes reveal recent viral structure in Eurasia. Sci. Adv. 8, eabo4435 (2022).
pubmed: 35895820 pmcid: 9328674 doi: 10.1126/sciadv.abo4435
Weinert, L. A. et al. Rates of vaccine evolution show strong effects of latency: implications for varicella zoster virus epidemiology. Mol. Biol. Evol. 32, 1020–1028 (2015).
pubmed: 25568346 pmcid: 4379407 doi: 10.1093/molbev/msu406
Pontremoli, C., Forni, D., Clerici, M., Cagliani, R. & Sironi, M. Possible European origin of circulating varicella zoster virus strains. J. Infect. Dis. https://doi.org/10.1093/infdis/jiz227 (2019).
Mammas, I. N. & Spandidos, D. A. Paediatric virology in the hippocratic corpus. Exp. Ther. Med. 12, 541–549 (2016).
pubmed: 27446241 pmcid: 4950906 doi: 10.3892/etm.2016.3420
Tian, C. et al. Genome-wide association and HLA region fine-mapping studies identify susceptibility loci for multiple common infections. Nat. Commun. 8, 599 (2017).
pubmed: 28928442 pmcid: 5605711 doi: 10.1038/s41467-017-00257-5
Krause-Kyora, B. et al. Ancient DNA study reveals HLA susceptibility locus for leprosy in medieval Europeans. Nat. Commun. 9, 1569 (2018).
pubmed: 29717136 pmcid: 5931558 doi: 10.1038/s41467-018-03857-x
Wallin, M. T. et al. The prevalence of MS in the United States: a population-based estimate using health claims data. Neurology 92, e1029–e1040 (2019).
pubmed: 30770430 pmcid: 6442006 doi: 10.1212/WNL.0000000000007035
Feigin, V. L. et al. Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 18, 459–480 (2019).
doi: 10.1016/S1474-4422(18)30499-X
Fleming, J. & Fabry, Z. The hygiene hypothesis and multiple sclerosis. Ann. Neurol. 61, 85–89 (2007).
pubmed: 17315205 doi: 10.1002/ana.21092
Listing, J., Gerhold, K. & Zink, A. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology 52, 53–61 (2013).
pubmed: 23192911 doi: 10.1093/rheumatology/kes305
Nielen, M. M. J. et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 50, 380–386 (2004).
pubmed: 14872479 doi: 10.1002/art.20018
Rubinacci, S., Ribeiro, D. M., Hofmeister, R. J. & Delaneau, O. Efficient phasing and imputation of low-coverage sequencing data using large reference panels. Nat. Genet. 53, 120–126 (2021).
pubmed: 33414550 doi: 10.1038/s41588-020-00756-0
Meyer, M. & Kircher, M. Illumina sequencing library preparation for highly multiplexed target capture and sequencing. Cold Spring Harb. Protoc. 2010, pdb.prot5448 (2010).
pubmed: 20516186 doi: 10.1101/pdb.prot5448
Schubert, M., Lindgreen, S. & Orlando, L. AdapterRemoval v2: rapid adapter trimming, identification, and read merging. BMC Res. Notes 9, 88 (2016).
pubmed: 26868221 pmcid: 4751634 doi: 10.1186/s13104-016-1900-2
Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009).
pubmed: 19451168 pmcid: 2705234 doi: 10.1093/bioinformatics/btp324
Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
pubmed: 19505943 pmcid: 2723002 doi: 10.1093/bioinformatics/btp352
Jónsson, H., Ginolhac, A., Schubert, M., Johnson, P. L. F. & Orlando, L. mapDamage2.0: fast approximate Bayesian estimates of ancient DNA damage parameters. Bioinformatics 29, 1682–1684 (2013).
pubmed: 23613487 pmcid: 3694634 doi: 10.1093/bioinformatics/btt193
Fu, Q. et al. A revised timescale for human evolution based on ancient mitochondrial genomes. Curr. Biol. 23, 553–559 (2013).
pubmed: 23523248 pmcid: 5036973 doi: 10.1016/j.cub.2013.02.044
Korneliussen, T. S., Albrechtsen, A. & Nielsen, R. ANGSD: analysis of next generation sequencing data. BMC Bioinformatics 15, 356 (2014).
pubmed: 25420514 pmcid: 4248462 doi: 10.1186/s12859-014-0356-4
Monroy Kuhn, J. M., Jakobsson, M. & Günther, T. Estimating genetic kin relationships in prehistoric populations. PLoS ONE 13, e0195491 (2018).
pubmed: 29684051 pmcid: 5912749 doi: 10.1371/journal.pone.0195491
Weissensteiner, H. et al. HaploGrep 2: mitochondrial haplogroup classification in the era of high-throughput sequencing. Nucleic Acids Res. 44, W58–W63 (2016).
pubmed: 27084951 pmcid: 4987869 doi: 10.1093/nar/gkw233
Scorrano, G., Yediay, F. E., Pinotti, T., Feizabadifarahani, M. & Kristiansen, K. The genetic and cultural impact of the steppe migration into Europe. Ann. Hum. Biol. 48, 223–233 (2021).
pubmed: 34459341 doi: 10.1080/03014460.2021.1942984
Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).
pubmed: 17701901 pmcid: 1950838 doi: 10.1086/519795
Shringarpure, S. S., Bustamante, C. D., Lange, K. & Alexander, D. H. Efficient analysis of large datasets and sex bias with ADMIXTURE. BMC Bioinformatics 17, 218 (2016).
pubmed: 27216439 pmcid: 4877806 doi: 10.1186/s12859-016-1082-x
Patterson, N. et al. Ancient admixture in human history. Genetics 192, 1065–1093 (2012).
pubmed: 22960212 pmcid: 3522152 doi: 10.1534/genetics.112.145037
Lawson, D. J., Hellenthal, G., Myers, S. & Falush, D. Inference of population structure using dense haplotype data. PLoS Genet. 8, e1002453 (2012).
pubmed: 22291602 pmcid: 3266881 doi: 10.1371/journal.pgen.1002453
Margaryan, A. et al. Population genomics of the Viking world. Nature 585, 390–396 (2020).
pubmed: 32939067 doi: 10.1038/s41586-020-2688-8
Hellenthal, G. et al. A genetic atlas of human admixture history. Science 343, 747–751 (2014).
pubmed: 24531965 pmcid: 4209567 doi: 10.1126/science.1243518
1000 Genomes Project Consortium et al. A global reference for human genetic variation. Nature 526, 68–74 (2015).
doi: 10.1038/nature15393
Myers, T. A., Chanock, S. J. & Machiela, M. J. LDlinkR: an R package for rapidly calculating linkage disequilibrium statistics in diverse populations. Front. Genet. 11, 157 (2020).
pubmed: 32180801 pmcid: 7059597 doi: 10.3389/fgene.2020.00157
Ishigaki, K. et al. Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis. Nature Genet. 54, 1640–1651 (2022).
Alekseyenko, A. V. et al. Causal graph-based analysis of genome-wide association data in rheumatoid arthritis. Biol. Direct 6, 25 (2011).
pubmed: 21592391 pmcid: 3118953 doi: 10.1186/1745-6150-6-25
Raychaudhuri, S. et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat. Genet. 44, 291–296 (2012).
pubmed: 22286218 pmcid: 3288335 doi: 10.1038/ng.1076
RACI consortium et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506, 376–381 (2014).
doi: 10.1038/nature12873
Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. GigaScience 4, 7 (2015).
pubmed: 25722852 pmcid: 4342193 doi: 10.1186/s13742-015-0047-8
Ju, D. & Mathieson, I. The evolution of skin pigmentation-associated variation in West Eurasia. Proc. Natl Acad. Sci. USA 118, e2009227118 (2021).
pubmed: 33443182 doi: 10.1073/pnas.2009227118
Nelson, R. M., Wallberg, A., Simões, Z. L. P., Lawson, D. J. & Webster, M. T. Genomewide analysis of admixture and adaptation in the Africanized honeybee. Mol. Ecol. 26, 3603–3617 (2017).
pubmed: 28378497 doi: 10.1111/mec.14122
Kolberg, L., Raudvere, U., Kuzmin, I., Vilo, J. & Peterson, H. gprofiler2—an R package for gene list functional enrichment analysis and namespace conversion toolset g:Profiler. F1000Res 9, ELIXIR-709 (2020).
pubmed: 33564394 pmcid: 7859841 doi: 10.12688/f1000research.24956.2
Thorndike, R. L. Who belongs in the family? Psychometrika 18, 267–276 (1953).
doi: 10.1007/BF02289263
Berg, J. J. & Coop, G. A population genetic signal of polygenic adaptation. PLoS Genet. 10, e1004412 (2014).
pubmed: 25102153 pmcid: 4125079 doi: 10.1371/journal.pgen.1004412
Frangos, C. C. & Schucany, W. R. Jackknife estimation of the bootstrap acceleration constant. Comput. Stat. Data Anal. 9, 271–281 (1990).
doi: 10.1016/0167-9473(90)90109-U
Sarmanova, A., Morris, T. & Lawson, D. J. Population stratification in GWAS meta-analysis should be standardized to the best available reference datasets. Preprint at bioRxiv https://doi.org/10.1101/2020.09.03.281568 (2020).
McFadden, D. in Frontiers in Econometrics 105–142 (Academic, 1973).
Efron, B. Bootstrap methods: another look at the jackknife. Ann. Stat. 7, 1–26 (1979).
doi: 10.1214/aos/1176344552
Kass, R. E. & Wasserman, L. A reference Bayesian test for nested hypotheses and its relationship to the Schwarz criterion. J. Am. Stat. Assoc. 90, 928–934 (1995).
doi: 10.1080/01621459.1995.10476592
Slatkin, M. Linkage disequilibrium—understanding the evolutionary past and mapping the medical future. Nat. Rev. Genet. 9, 477–485 (2008).
pubmed: 18427557 pmcid: 5124487 doi: 10.1038/nrg2361

Auteurs

William Barrie (W)

Department of Zoology, University of Cambridge, Cambridge, UK.
Department of Genetics, University of Cambridge, Cambridge, UK.

Yaoling 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.

Evan K Irving-Pease (EK)

Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.

Kathrine E Attfield (KE)

Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.

Gabriele Scorrano (G)

Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.

Lise Torp 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.

Angelos P Armen (AP)

Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.

Evangelos Antonios Dimopoulos (EA)

Pathogen Genomics and Evolution Group, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.

Aaron Stern (A)

Departments of Integrative Biology and Statistics, University of California, Berkeley, Berkeley, CA, USA.

Alba Refoyo-Martinez (A)

Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.

Alice Pearson (A)

Department of Genetics, University of Cambridge, Cambridge, UK.

Abigail Ramsøe (A)

Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.

Charleen Gaunitz (C)

Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.

Fabrice 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.

Marie Louise S Jørkov (MLS)

Laboratory of Biological Anthropology, Department of Forensic Medicine, University of Copenhagen, Copenhagen, Denmark.

Stig Bermann Møller (SB)

Ålborg Historiske Museum, Nordjyske Museer, Vestbjerg, Denmark.

Bente Springborg (B)

Ålborg Historiske Museum, Nordjyske Museer, Vestbjerg, Denmark.

Lutz Klassen (L)

Museum Østdanmark-Djursland og Randers, Randers, Denmark.

Inger Marie Hyldgård (IM)

Museum Østdanmark-Djursland og Randers, Randers, Denmark.

Niels Wickmann (N)

Museum Vestsjælland, Holbæk, Denmark.

Lasse Vinner (L)

Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.

Thorfinn Sand Korneliussen (TS)

Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.

Morten E 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.

Martin Sikora (M)

Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.

Kristian Kristiansen (K)

Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.
Department of Historical Studies, University of Gothenburg, Gothenburg, Sweden.

Santiago Rodriguez (S)

MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, UK.

Rasmus 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.

Astrid K N 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.

Daniel J 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.

Lars 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.

Eske 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.

Classifications MeSH