The major genetic risk factor for severe COVID-19 is inherited from Neanderthals
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Abstract
A recent genetic association study 1 identified a gene cluster on chromosome 3 as a risk locus for respiratory failure after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A separate study (COVID-19 Host Genetics Initiative)2 comprising 3,199 hospitalized patients with coronavirus disease 2019 (COVID-19) and control individuals showed that this cluster is the major genetic risk factor for severe symptoms after SARS-CoV-2 infection and hospitalization. Here we show that the risk is conferred by a genomic segment of around 50 kilobases in size that is inherited from Neanderthals and is carried by around 50% of people in south Asia and around 16% of people in Europe.
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Some loci introgressed from archaic hominins in present-day populations appear to influence disease risk, such as neurological, psychiatric, immunological, dermatological, and dietary disorders, either positively or negatively.
“in present-day populations, some loci introgressed from archaic hominins appear to influence disease risk, such as neurological, psychiatric, immunological, dermatological, and dietary disorders (5, 58), either positively or negatively.”
From Past human expansions shaped the spatial pattern of Neanderthal ancestry (2023) · cites this paper as [58]
The main text reports that a Neanderthal-derived haplotype may contribute to severe COVID-19 risk in present-day populations, supporting an example of increased infectious-disease risk. It does not establish effects on neurological, psychiatric, dermatological, or dietary disorders, or show that introgressed loci can reduce disease risk. Its discussion of positive selection is not evidence of reduced disease risk. (LLM, conf=0.86)
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Cites
Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., Xiang, J., Wang, Y., Song, B., Gu, X., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30566-3 · Cited by 27,263 · see citing works
Guindon, S., Dufayard, J.-F., Lefort, V., Anisimova, M., Hordijk, W., & Gascuel, O. (2010) · Systematic Biology · doi:10.1093/sysbio/syq010 · Cited by 18,376 · see citing works
A global reference for human genetic variation
The 1000 Genomes Project Consortium, authors, C., Auton, A., Abecasis, G. R., Steering committee, Altshuler, D. M., Durbin, R. M., Abecasis, G. R., Bentley, D. R., Chakravarti, A., et al. (2015) · Nature · doi:10.1038/nature15393 · Cited by 18,247 · see citing works
Second-generation PLINK: rising to the challenge of larger and richer datasets
Chang, C. C., Chow, C. C., Tellier, L. C., Vattikuti, S., Purcell, S. M., & Lee, J. J. (2015) · Gigascience · doi:10.1186/s13742-015-0047-8 · Cited by 12,709 · see citing works
Dating of the human–ape splitting by a molecular clock of mitochondrial DNA.
Hasegawa, M., Kishino, H., & Yano, T.-A. (1985) · Journal of Molecular Evolution · doi:10.1007/bf02101694 · Cited by 8,687 · see citing works
A draft sequence of the Neandertal genome
Green, R. E., Krause, J., Briggs, A. W., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M. H.-Y., et al. (2010) · Science · doi:10.1126/science.1188021 · Cited by 4,318 · see citing works
Self-citationThe complete genome sequence of a Neanderthal from the Altai Mountains
Prüfer, K., Racimo, F., Patterson, N., Jay, F., Sankararaman, S., Sawyer, S., Heinze, A., Renaud, G., Sudmant, P. H., de Filippo, C., et al. (2014) · Nature · doi:10.1038/nature12886 · Cited by 2,254 · see citing works
Self-citationMachiela, M. J., & Chanock, S. J. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv402 · Cited by 2,069 · see citing works
Genomewide Association Study of Severe Covid-19 with Respiratory Failure
The Severe Covid-19 GWAS Group (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2020283 · Cited by 1,986 · see citing works
A high-coverage genome sequence from an archaic denisovan individual
Meyer, M., Kircher, M., Gansauge, M.-T., Li, H., Racimo, F., Mallick, S., Schraiber, J. G., Jay, F., Prüfer, K., de Filippo, C., et al. (2012) · Science · doi:10.1126/science.1224344 · Cited by 1,967 · see citing works
Self-citationA high-resolution recombination map of the human genome
Kong, A., Gudbjartsson, D. F., Sainz, J., Jonsdottir, G. M., Gudjonsson, S. A., Richardsson, B., Sigurdardottir, S. L., Barnard, J., Hallbeck, B., Másson, G., et al. (2002) · Nature Genetics · doi:10.1038/ng917 · Cited by 1,750 · see citing works
Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA
Huerta-Sánchez, E., Jin, X., Asan, Bianba, Z., Peter, B. M., Vinckenbosch, N., Liang, Y., Yi, X., He, M., Somel, M., et al. (2014) · Nature · doi:10.1038/nature13408 · Cited by 1,208 · see citing works
Yates, A. D., Achuthan, P., Akanni, W. A., Allen, J., Allen, J., Álvarez-Jarreta, J., Amode, M. R., Armean, I. M., Azov, A. G., Bennett, R., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz966 · Cited by 1,162 · see citing works
The genomic landscape of Neanderthal ancestry in present-day humans
Sankararaman, S., Mallick, S., Dannemann, M., Prüfer, K., Kelso, J., Pääbo, S., Patterson, N., & Reich, D. (2014) · Nature · doi:10.1038/nature12961 · Cited by 1,107 · see citing works
Self-citationInitiative, T. C.-1. H. G. (2020) · European Journal of Human Genetics · doi:10.1038/s41431-020-0636-6 · Cited by 746 · see citing works
A high-coverage Neandertal genome from Vindija Cave in Croatia
Prüfer, K., de Filippo, C., Grote, S., Mafessoni, F., Korlević, P., Hajdinjak, M., Vernot, B., Skov, L., Hsieh, P., Peyrégne, S., et al. (2017) · Science · doi:10.1126/science.aao1887 · Cited by 719 · see citing works
Self-citationLangergraber, K. E., Prüfer, K., Rowney, C., Boesch, C., Crockford, C., Fawcett, K. A., Inoue, E., Inoue-Muruyama, M., Mitani, J. C., Muller, M. N., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211740109 · Cited by 638 · see citing works
Self-citationTabix: fast retrieval of sequence features from generic TAB-delimited files
Li, H. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btq671 · Cited by 575 · see citing works
Resurrecting Surviving Neandertal Lineages from Modern Human Genomes
Vernot, B., & Akey, J. M. (2014) · Science · doi:10.1126/science.1245938 · Cited by 562 · see citing works
Heterochromatin protein 1α interacts with parallel RNA and DNA G-quadruplexes
Roach, R. J., Garavís, M., González, C., Jameson, G. B., Filichev, V. V., & Hale, T. K. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1138 · Cited by 520 · see citing works
The Date of Interbreeding between Neandertals and Modern Humans
Sankararaman, S., Patterson, N., Li, H., Pääbo, S., & Reich, D. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002947 · Cited by 460 · see citing works
Self-citationExcavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals
Vernot, B., Tucci, S., Kelso, J., Schraiber, J. G., Wolf, A. B., Gittelman, R. M., Dannemann, M., Grote, S., McCoy, R. C., Norton, H., et al. (2016) · Science · doi:10.1126/science.aad9416 · Cited by 459 · see citing works
Self-citationAnalysis of Human Sequence Data Reveals Two Pulses of Archaic Denisovan Admixture
Browning, S. R., Browning, B. L., Zhou, Y., Tucci, S., & Akey, J. M. (2018) · Cell · doi:10.1016/j.cell.2018.02.031 · Cited by 381 · see citing works
A high-coverage Neandertal genome from Chagyrskaya Cave
Mafessoni, F., Grote, S., de Filippo, C., Slon, V., Kolobova, K. A., Viola, B., Markin, S. V., Chintalapati, M., Peyrégne, S., Skov, L., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2004944117 · Cited by 309 · see citing works
Self-citationVetter, P., Vu, D., L’Huillier, A. G., Schibler, M., Kaiser, L., & Jacquérioz, F. (2020) · BMJ · doi:10.1136/bmj.m1470 · Cited by 275 · see citing works
Identifying and Interpreting Apparent Neanderthal Ancestry in African Individuals
Chen, L., Wolf, A. B., Fu, W., Li, L., & Akey, J. M. (2020) · Cell · doi:10.1016/j.cell.2020.01.012 · Cited by 254 · see citing works
Dannemann, M., Andrés, A. M., & Kelso, J. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.11.015 · Cited by 249 · see citing works
Archaic Hominin Admixture Facilitated Adaptation to Out-of-Africa Environments
Gittelman, R. M., Schraiber, J. G., Vernot, B., Mikacenic, C., Wurfel, M. M., & Akey, J. M. (2016) · Current Biology · doi:10.1016/j.cub.2016.10.041 · Cited by 181 · see citing works
The nature of Neanderthal introgression revealed by 27,566 Icelandic genomes
Skov, L., Coll Macià, M., Sveinbjörnsson, G., Mafessoni, F., Lucotte, E. A., Einarsdóttir, M. S., Jonsson, H., Halldorsson, B., Gudbjartsson, D. F., Helgason, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2225-9 · Cited by 145 · see citing works
Model‐based detection and analysis of introgressed Neanderthal ancestry in modern humans
Steinrücken, M., Spence, J. P., Kamm, J. A., Wieczorek, E., & Song, Y. S. (2018) · Molecular Ecology · doi:10.1111/mec.14565 · Cited by 73 · see citing works
A high-coverage Neandertal genome from Chagyrskaya CavePreprint
Mafessoni, F., Grote, S., de Filippo, C., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.12.988956 · Cited by 51 · see citing works
A Neanderthal Sodium Channel Increases Pain Sensitivity in Present-Day Humans
Zeberg, H., Dannemann, M., Sahlholm, K., Tsuo, K., Maričić, T., Wiebe, V., Hevers, W., Robinson, H. P. C., Kelso, J. F., & Pääbo, S. (2020) · Current Biology · doi:10.1016/j.cub.2020.06.045 · Cited by 50 · see citing works
Self-citationThe Neandertal Progesterone Receptor
Zeberg, H., Kelso, J. F., & Pääbo, S. (2020) · Molecular Biology and Evolution · doi:10.1093/molbev/msaa119 · Cited by 48 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
COVID-19 and the human innate immune system
Schultze, J. L., & Aschenbrenner, A. C. (2021) · Cell · doi:10.1016/j.cell.2021.02.029 · Cited by 714 · see citing works
The Human Pangenome Project: a global resource to map genomic diversity
Wang, T., Antonacci-Fulton, L., Howe, K., Lawson, H. A., Lucas, J. K., Phillippy, A. M., Popejoy, A. B., Asri, M., Carson, C., Chaisson, M. J. P., et al. (2022) · Nature · doi:10.1038/s41586-022-04601-8 · Cited by 494 · see citing works
The influence of evolutionary history on human health and disease
Benton, M. L., Abraham, A., LaBella, A. L., Abbot, P., Rokas, A., & Capra, J. A. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-020-00305-9 · Cited by 291 · see citing works
Human immune diversity: from evolution to modernity
Liston, A., Humblet-Baron, S., Duffy, D., & Goris, A. (2021) · Nature Immunology · doi:10.1038/s41590-021-01058-1 · Cited by 187 · see citing works
Nachega, J. B., Atteh, R., Ihekweazu, C., Sam-Agudu, N. A., Adejumo, P., Nsanzimana, S., Rwagasore, E., Condo, J., Paleker, M., Mahomed, H., et al. (2021) · The American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.21-0033 · Cited by 104 · see citing works
The evolutionary history of human spindle genes includes back-and-forth gene flow with Neandertals
Peyrégne, S., Kelso, J., Peter, B. M., & Pääbo, S. (2022) · eLife · doi:10.7554/elife.75464 · Cited by 24 · see citing works
Self-citationPast human expansions shaped the spatial pattern of Neanderthal ancestry
Quilodrán, C. S., Rio, J., Tsoupas, A., & Currat, M. (2023) · Science Advances · doi:10.1126/sciadv.adg9817 · Cited by 12 · see citing works
- Authors
- Zeberg, H., & Pääbo, S.
- Affiliations
- Karolinska Institutet (SE)
- Okinawa Institute of Science and Technology Graduate University (JP)
- Corresponding author
- Zeberg, Hugo
- Pääbo, Svante
- Venue
- Nature
- Published
- 2020-09-30
- Volume
- 587
- Issue
- 7835
- Pages
- 610-612
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3090928025
- Cited by
- 636
- References
- 33
- Citations by year
- 2026: 24 · 2025: 36 · 2024: 77 · 2023: 97 · 2022: 123 · 2021: 214 · 2020: 64
- FWCI
- 73.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (210561/Z/18/Z)
- Max-Planck-Gesellschaft
- NordForsk
- NOMIS Stiftung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- severe COVID-19, SARS-CoV-2, Neanderthal DNA, introgression, genetic susceptibility loci, chromosome 3, respiratory failure, population ancestry, South Asian populations, European populations
- MeSH terms
- COVID-19, Animals, Asia, Chromosomes, Human, Pair 3, Europe, Multigene Family, Haplotypes, Hospitalization, Humans, Phylogeny, Genetic Variation, Linkage Disequilibrium, Case-Control Studies, Genetic Predisposition to Disease, Severe Acute Respiratory Syndrome, Genome-Wide Association Study, Neanderthals
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