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

Background The 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. Methods The 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 Sanger’s 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. Results The 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. Conclusion The 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Hassan II Academy of Science and Technology (Morocco) provided funding. They had no role in study design, data analysis or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from the ethics committee of Cheikh Zaid Hospital of Rabat (ref. no.: CEFCZ/AB/PR_RFG). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as [ClinicalTrials.gov][1]. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable All relevant data are within the manuscript and its Supporting Information files. [1]: http://ClinicalTrials.gov