A genomic region associated with protection against severe COVID-19 is inherited from Neandertals

@article{Zeberg2021AGR,
  title={A genomic region associated with protection against severe COVID-19 is inherited from Neandertals},
  author={Hugo Zeberg and Svante P{\"a}{\"a}bo},
  journal={Proceedings of the National Academy of Sciences},
  year={2021},
  volume={118}
}
  • H. Zeberg, S. Pääbo
  • Published 15 February 2021
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences
Significance We show that a haplotype on chromosome 12, which is associated with a ∼22% reduction in relative risk of becoming severely ill with COVID-19 when infected by SARS-CoV-2, is inherited from Neandertals. This haplotype is present at substantial frequencies in all regions of the world outside Africa. The genomic region where this haplotype occurs encodes proteins that are important during infections with RNA viruses. It was recently shown that the major genetic risk factor associated… 

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References

SHOWING 1-10 OF 49 REFERENCES
The major genetic risk factor for severe COVID-19 is inherited from Neanderthals
TLDR
Risk of severe COVID-19 is conferred by a genomic segment that is inherited from Neanderthals and is carried by around 50% and 16% of people in south Asia and Europe, respectively.
Genomewide Association Study of Severe Covid-19 with Respiratory Failure
TLDR
A 3p21.31 gene cluster is identified as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and a potential involvement of the ABO blood-group system is confirmed.
Genetic Variation in OAS1 Is a Risk Factor for Initial Infection with West Nile Virus in Man
TLDR
OAS1 SNP rs10774671 is identified as a host genetic risk factor for initial infection with WNV in humans and tested the effect of this SNP on viral replication in a novel ex vivo model of WNV infection in primary human lymphoid tissue.
Genetic mechanisms of critical illness in Covid-19
The subset of patients who develop critical illness in Covid-19 have extensive inflammation affecting the lungs and are strikingly different from other patients: immunosuppressive therapy benefits
Association of SARS susceptibility with single nucleic acid polymorphisms of OAS1 and MxA genes: a case-control study
TLDR
SNPs in the OAS1 3'-UTR and MxA promoter region appear associated with host susceptibility to SARS in Chinese Han population.
Neandertal origin of genetic variation at the cluster of OAS immunity genes.
TLDR
DNA sequence variation in the OAS gene cluster on chromosome 12 is surveyed and strong evidence that a haplotype extending for ~185 kb introgressed from Neandertals is provided, consistent with neutral introgression.
Genomic Signatures of Selective Pressures and Introgression from Archaic Hominins at Human Innate Immunity Genes.
The phenotypic legacy of admixture between modern humans and Neandertals
TLDR
It is established that archaic admixture influences disease risk in modern humans, hypotheses about the effects of hundreds of Neandertal haplotypes are provided, and the utility of EHR data in evolutionary analyses is demonstrated.
...
1
2
3
4
5
...