We show that the DUP4 variant is associated with hemoglobin levels in a community setting indicating protection from malaria. Low levels of hemoglobin indicate anemia, which can reflect sub-clinical levels of malaria infection, and the village studied has a very high prevalence of P. falciparum infection, so our study supports the importance of the DUP4 variant in malaria protection. However, the absence of an association with either the number of clinical episodes of malaria or the parasite load is perhaps more puzzling. This may reflect the lower heritability of these traits compared to hemoglobin levels, and therefore the increased effect of non-genetic variation (Table 1). A recent case-control study of severe malaria in Kenyan children found an association of DUP4 with higher hemoglobin levels but not with parasite load, repeating the results we present here.39 How DUP4 protects against malaria is unknown and alternatively these results may point to a role in directly affecting erythrocyte invasion by the parasite, which is detectable in our cohort, rather than the more general phenotypes such as number of clinical malaria episodes or parasite load.