The Neanderthal‐Derived 3p21 Haplotype at LZTFL1 in Modern‐Day Moroccans Is Associated With COVID‐19 Severity and Further Suggests the Presence of Neanderthals in North Africa

ABSTRACT

There is considerable variability in the clinical presentation of COVID‐19 among patients infected with SARS‐CoV‐2. Genome‐wide association studies (GWASs) have identified the 12q24.13 and 3p21.31 regions, derived from Neanderthal DNA, as the human genetic loci most strongly associated with COVID‐19 severity. We examined in this study the 3p locus in the Moroccan population by analysing allele and haplotype frequencies at the LZTFL1 gene and their associations with COVID‐19 outcomes. Three SNPs at LZTFL1 , tagging the Neanderthal‐derived COVID‐19 risk haplotype, were sequenced by Sanger's method in 102 ambulatory participants and 105 hospitalized patients and have been compared to 118 controls negative for SARS‐CoV‐2 infection using logistic regression analysis. Results showed that the prevalence of the lead variant rs11385942 in this locus was 8.9%, whereas the variants rs35044562 and rs13078854, which tag the Neanderthal haplotype, were present in only 6.3%. Our study showed that only the rs35044562‐T and rs13078854‐A alleles were associated with a 2.5‐fold increased risk of severe COVID‐19 ( p  = 0.028). These two alleles, in LD with the rs11385942‐AA one, form the haplotype inherited from the Neanderthal, the only haplotype associated with COVID‐19 severity in the Moroccan population ( p  = 0.030), whereas sub‐Saharan African and the rare local haplotype also containing the rs11385942 variant do not influence the COVID‐19 outcomes 19 ( p  > 0.05). Furthermore, our study showed that the Neanderthal haplotype at 3p21 locus exists in the inhabitants of Morocco at a frequency close to that of Europeans and suggests a close connection between North Africa and Eurasia.