Abstract
It was recently shown that the major genetic risk factor associated with becoming severely ill with COVID-19 when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is inherited from Neandertals. New, larger genetic association studies now allow additional genetic risk factors to be discovered. Using data from the Genetics of Mortality in Critical Care (GenOMICC) consortium, we show that a haplotype at a region on chromosome 12 associated with requiring intensive care when infected with the virus is inherited from Neandertals. This region encodes proteins that activate enzymes that are important during infections with RNA viruses. In contrast to the previously described Neandertal haplotype that increases the risk for severe COVID-19, this Neandertal haplotype is protective against severe disease. It also differs from the risk haplotype in that it has a more moderate effect and occurs at substantial frequencies in all regions of the world outside Africa. Among ancient human genomes in western Eurasia, the frequency of the protective Neandertal haplotype may have increased between 20,000 and 10,000 y ago and again during the past 1,000 y.
Highlights
Neandertals evolved in western Eurasia about half a million years ago and subsequently lived largely separated from the ancestors of modern humans in Africa [1], limited gene flow from Africa is likely to have occurred [2,3,4,5]
We investigated whether the index single-nucleotide polymorphisms (SNPs), that is, the SNPs with the strongest association (Materials and Methods), at the seven loci associated with risk of requiring intensive care upon SARS-CoV-2 infection on chromosomes 6, 12, 19, and 21 [22] harbor Neandertal-like alleles
We find that the SNPs in the chromosome 12 locus associated with COVID-19 hospitalization (P < 1.0e-5; Fig. 1) are in linkage disequilibrium (LD) (r2 ≥ 0.8) in Europeans and form a haplotype
Summary
Neandertals evolved in western Eurasia about half a million years ago and subsequently lived largely separated from the ancestors of modern humans in Africa [1], limited gene flow from Africa is likely to have occurred [2,3,4,5]. Neandertals as well as Denisovans, their Asian sister group, became extinct about 40,000 y ago [6] They continue to have a biological impact on human physiology today through genetic contributions to modern human populations that occurred during the last tens of thousands of years of their existence It was shown that a haplotype in a region on chromosome 3 is associated with becoming critically ill upon infection with the novel severe acute respiratory coronavirus 2 (SARS-CoV-2) [19] and was contributed to modern humans by Neandertals [20]. We show that, at one of these loci, a haplotype associated with reduced risk of becoming severely ill upon SARS-CoV-2 infection is derived from Neandertals
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