Study of the protectiveOAS1rs10774671-G allele against severe COVID-19 in Moroccans suggests a North African origin for Neanderthals

Abstract

32 Background: The clinical presentation of COVID-19 has shown high variability 33 between individuals, which is partly due to genetic factors. The OAS1/2/3 cluster 34 was found to be strongly associated with COVID-19 severity. We aimed to 35 examine this locus for the occurrence of the critical variant, rs10774671, and its 36 respective haplotype blocks within the Moroccan population. 37 Methods: The frequency of SNPs at the cluster of OAS immunity genes was 38 assessed from an in-house database in 157 unrelated individuals of Moroccan 39 origin. The OAS1 exon 6 was sequenced by Sanger's method in 71 40 asymptomatic/mild and 74 moderate/severe individuals positive for SARS-CoV- 41 2. Genotypic, allelic, and haplotype frequencies of three SNPs were compared 42 between the two groups. Finally, males in our COVID-19 series were genotyped 43 for the Berber-specific marker E-M81. 44 Results: The prevalence of the OAS1 rs10774671-G allele in present-day 45 Moroccans was 40.4%, close to that of Europeans. However, it was found equally 46 on both the Neanderthal GGG haplotype and the African GAC haplotype with a 47 frequency of 20% each. These two haplotypes, and hence the rs10774671-G 48 allele, were significantly associated with the protection against severe COVID-19 49 (p = 0.034, p = 0.041, and p = 0.008 respectively). Surprisingly, among Berber 50 men, the African haplotype was absent while the prevalence of the Neanderthal 51 haplotype was close to that of Europeans. 52 Conclusion: The protective rs10774671-G allele of OAS1 was found only in the medRxiv preprint doi: https://doi.org/10.1101/2023.08.19.23294314; this version posted August 22, 2023. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . 53 Neanderthal haplotype in Berbers, the indigenous people of North Africa, 54 suggesting that this region may have served as the stepping-stone for the passage 55 of the hominids to the other continents. 56 57 58 Keywords: SARS-CoV-2, COVID-19 severity, 2’,5’-oligoadenylate synthetase, 59 single nucleotide polymorphism, Neanderthals, North Africa 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 medRxiv preprint doi: https://doi.org/10.1101/2023.08.19.23294314; this version posted August 22, 2023. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . 75