Of the 13 single nucleotides polymorphisms constituting the core haplotype, 11 occur in a homozygous form in the Vindija 33.19 Neanderthal (Fig. We found that the risk alleles of both of these variants are present in a homozygous form in the genome of the Vindija 33.19 Neanderthal, an approximately 50,000-year-old Neanderthal from Croatia in southern Europe 8. The index variants of the two studies 1, 2 are in high linkage disequilibrium ( r 2 > 0.98) in non-African populations (Extended Data Fig.
We therefore investigated whether the haplotype may have come from Neanderthals or Denisovans. Some such long haplotypes have entered the human population by gene flow from Neanderthals or Denisovans, extinct hominins that contributed genetic variants to the ancestors of present-day humans around 40,000–60,000 years ago 6, 7. This ‘core’ haplotype is furthermore in weaker linkage disequilibrium with longer haplotypes of up to 333.8 kb ( r 2 > 0.32) (Extended Data Fig. The genetic variants that are most associated with severe COVID-19 on chromosome 3 (45,859,651–45,909,024 (hg19)) are all in high linkage disequilibrium (LD)-that is, they are all strongly associated with each other in the population ( r 2 > 0.98)-and span 49.4 thousand bases (kb) (Fig. The risk variant in this region confers an odds ratio for requiring hospitalization of 1.6 (95% confidence interval, 1.42–1.79) (Extended Data Fig. Recently, a dataset was released by the COVID-19 Host Genetics Initiative in which the region on chromosome 3 is the only region that is significantly associated with severe COVID-19 at the genome-wide level (Fig. A previous study 1 identified two genomic regions that are associated with severe COVID-19: one region on chromosome 3, which contains six genes, and one region on chromosome 9 that determines ABO blood groups. Thus, genetic risk factors may have a role in disease progression. These risk factors, however, do not fully explain why some people have no or mild symptoms whereas others have severe symptoms. Early in the pandemic, it became clear that advanced age is a major risk factor, as well as being male and some co-morbidities 5.
The clinical manifestations of the disease caused by the virus, SARS-CoV-2, vary widely in severity, ranging from no or mild symptoms to rapid progression to respiratory failure 4. The COVID-19 pandemic has caused considerable morbidity and mortality, and has resulted in the death of over a million people to date 3.
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