Association of Chromosome 3p21.32 Haplotype Blocks Introgressed from Neanderthals with Critical COVID-19 in a Spanish...

Human chromosome 3p21.31 variants introgressed from Neanderthals have been associated with a higher risk of developing a severe form of COVID-19. These Neanderthal DNA variants would regulate the expression of several genes, including LZTFL1 (implicated in the epithelial-mesenchymal transition) and proinflammatory chemokine receptors.

We studied three introgressed haplotypes in patients who developed critical COVID-19 (N = 446; 82 deaths), less severe non-critical COVID-19 (N = 552), and population controls (N = 500) from the region of Asturias, Northern Spain. All the participants were genotyped for six single nucleotide polymorphisms that defined the three 3p21.31 haplotypes.

For the haplotype in the LZTFL1 gene, the total patients were significantly higher frequency carriers of the Neanderthal variant compared to controls (24% vs. 17%; p < 0.05, OR = 1.53, 95% CI = 1.16-2.01). Multiple logistic regression showed that critical COVID-19 was independently associated with male sex, hypertension, dyslipaemia, and the introgressed LZTFL1 haplotype (p = 0.006). The frequency of these introgressed genotypes did not differ between normotensives and normolipaemics in the two patient groups but was significantly increased among hypertensives (p = 0.003) and dyslipaemics (p = 0.001).

In our population, the 3p21.31 haplotypes introgressed from Neanderthals were associated with increased risk of critical COVID-19, and the risk effect was higher among patients with hypertension and dyslipaemia.