A fourth locus in thePlasmodium falciparumgenome associated with sickle haemoglobin

Abstract

AbstractHeterozygosity for sickle haemoglobin (HbS) confers protection against severe malaria caused by the parasitePlasmodium falciparum. Recent work suggests that this protective effect can depend on the parasite genotype. Here, we performed a genome-wide association analysis ofP. falciparumagainst human β-globin genotypes in a sample of 1,368 people with mild malaria in northern Ghana. We replicated the previously identified associations with HbS at two parasite loci. However, a newly identified locus within the serine/threonine kinaseFIKK4.2, which we termPfsa4, was also associated with HbS; this finding replicated in a published sample from Mali. ThePfsa1-4mutations vary widely in frequencies across Africa, are absent from Asia, and are highly correlated with each-other across multiple populations. We found no strong associations with haemoglobin C. These findings add new complexity to the emerging picture of association between human and co-evolving malaria parasite genomes, suggesting new avenues for functional exploration.