Study of the protective OAS1 rs10774671-G allele against severe COVID-19 in Moroccans suggests a North African origin for Neanderthals

BackgroundThe clinical presentation of COVID-19 has shown high variability between individuals, which is partly due to genetic factors. The OAS1/2/3 cluster was found to be strongly associated with COVID-19 severity. We aimed to examine this locus for the occurrence of the critical variant, rs10774671, and its respective haplotype blocks within the Moroccan population. MethodsThe frequency of SNPs at the cluster of OAS immunity genes was assessed from an in-house database in 157 unrelated individuals of Moroccan origin. The OAS1 exon 6 was sequenced by Sangers method in 71 asymptomatic/mild and 74 moderate/severe individuals positive for SARS-CoV-2. Genotypic, allelic, and haplotype frequencies of three SNPs were compared between the two groups. Finally, males in our COVID-19 series were genotyped for the Berber-specific marker E-M81. ResultsThe prevalence of the OAS1 rs10774671-G allele in present-day Moroccans was 40.4%, close to that of Europeans. However, it was found equally on both the Neanderthal GGG haplotype and the African GAC haplotype with a frequency of 20% each. These two haplotypes, and hence the rs10774671-G allele, were significantly associated with the protection against severe COVID-19 (p = 0.034, p = 0.041, and p = 0.008 respectively). Surprisingly, among Berber men, the African haplotype was absent while the prevalence of the Neanderthal haplotype was close to that of Europeans. ConclusionThe protective rs10774671-G allele of OAS1 was found only in the Neanderthal haplotype in Berbers, the indigenous people of North Africa, suggesting that this region may have served as the stepping-stone for the passage of the hominids to the other continents.