The major genetic risk factor for severe COVID-19 is inherited from Neanderthals

  title={The major genetic risk factor for severe COVID-19 is inherited from Neanderthals},
  author={Hugo Zeberg and Svante P{\"a}{\"a}bo},
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… 
A genetic variant protective against severe COVID-19 is inherited from Neandertals
A Neandertal haplotype is protective against severe COVID-19, is of more moderate effect, and is found at substantial frequencies in all regions of the world outside Africa.
A genomic region associated with protection against severe COVID-19 is inherited from Neandertals
It is shown 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 and is present at substantial frequencies in all regions of the world outside Africa.
The major genetic risk factor for severe COVID-19 does not show any association among South Asian populations
It was found that the polymorphism present in the 50 kb introgressed genomic segment (rs10490770) did not show any significant correlation with the infection and case fatality rate in India, consistent with the real-time infection rate and casefatality rate among various states of India.
The major genetic risk factor for severe COVID-19 is associated with protection against HIV
  • H. Zeberg
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2022
It is shown that carriers of the risk variant have an ∼27% lower risk of HIV infection.
Mapping the human genetic architecture of COVID-19 by worldwide meta-analysis
Smoking and body mass index are identified as causal risk factors for severe COVID-19 and this working model of international collaboration is a blue-print for future genetic discoveries in the event of pandemics or for any complex human disease.
The major genetic risk factor for severe COVID-19 among Europeans does not show any association among Indian populations
This work found out that the polymorphism present in 50kb introgressed segment (rs10490770) did not show any significant correlation with the realtime infection and case fatality ratio in India.
The human genetic epidemiology of COVID-19
Important emergent opportunities include the clinical translatability of genetic risk prediction, the repurposing of existing drugs, exploration of variable host effects of different viral strains, study of inter-individual variability in vaccination response and understanding the long-term consequences of SARS-CoV-2 infection.
SARS-CoV-2 genetic variations associated with COVID-19 pathogenicity
It is found that the mutation 11 083G>T, located in the coding region of non-structural protein 6, is significantly associated with asymptomatic COVID-19, and patient age is positively correlated with symptomatic infection, while gender is not significantly correlated with the development of the disease.
Human genetic basis of coronavirus disease 2019
The human genetic basis could provide scientific bases for disease prediction and targeted therapy to address the COVID-19 scourge.


Genomewide Association Study of Severe Covid-19 with Respiratory Failure
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.
The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic
This initiative brings together the human genetics community to generate, share, and analyze data to learn the genetic determinants of COVID-19 susceptibility, severity, and outcomes, and contribute to global knowledge of the biology of SARS-CoV-2 infection and disease.
The landscape of Neandertal ancestry in present-day humans
The results suggest that part of the explanation for genomic regions of reduced Neanderthal ancestry is Neanderthal alleles that caused decreased fertility in males when moved to a modern human genetic background.
A Draft Sequence of the Neandertal Genome
The genomic data suggest that Neandertals mixed with modern human ancestors some 120,000 years ago, leaving traces of Ne andertal DNA in contemporary humans, suggesting that gene flow from Neand Bertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.
The Date of Interbreeding between Neandertals and Modern Humans
The extent of linkage disequilibrium (LD) in the genomes of present-day Europeans is measured and it is found that the last gene flow from Neandertals (or their relatives) into Europeans likely occurred 37,000–86,000 years before the present (BP), and most likely 47,000-65,000 year ago.
A high-coverage Neandertal genome from Vindija Cave in Croatia
The genome of a female Neandertal from ~50,000 years ago from Vindija Cave, Croatia, is sequenced to ~30-fold genomic coverage, allowing 10 to 20% more Ne andertal DNA to be identified in present-day humans, including variants involved in low-density lipoprotein cholesterol concentrations, schizophrenia, and other diseases.
Resurrecting Surviving Neandertal Lineages from Modern Human Genomes
Analyses of surviving archaic lineages suggest that there were fitness costs to hybridization, admixture occurred both before and after divergence of non-African modern humans, and Neandertals were a source of adaptive variation for loci involved in skin phenotypes.
The complete genome sequence of a Neandertal from the Altai Mountains
It is shown that interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene and a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans is established.