Genetic Risk Factor for Severe COVID-19

We next investigated whether the core 49.4-kb haplotype might be inherited by both Neanderthals and present-day people from the com- mon ancestors of the two groups that lived about 0.5 million years ago9. The longer a present-day human haplotype shared with Neanderthals is, the less likely it is to originate from the common ancestor, because recombination in each generation will tend to break up haplotypes into smaller segments. Assuming a generational time of 29 years12, the local recombination rate13 (0.53 cM per Mb), a split between Neanderthals and modern humans of 550,000 years9 and interbreeding between the two groups around 50,000 years ago, and using a published equation14, we exclude that the Neanderthal-like haplotype derives from the com- mon ancestor (P = 0.0009). For the 333.8-kb-long Neanderthal-like haplotype, the probability of an origin from the common ancestral population is even lower (P = 1.6 × 10−26). The risk haplotype thus entered the modern human population from Neanderthals. This is in agree- ment with several previous studies, which have identified gene flow from Neanderthals in this chromosomal region15–21 (Extended Data Table 2). The close relationship of the risk haplotype to the Vindija 33.19 Neanderthal is compatible with this Neanderthal being closer to the majority of the Neanderthals who contributed DNA to present-day people than the other two Neanderthals10.

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