We analyzed data from a longitudinal study of a population from the village of Nyamisati, in the Rufiji river delta, 150 km south of Dar-es-Salaam, Tanzania, described previously.29, 30, 31 This region was holoendemic for malaria, predominantly P. falciparum, which causes 99.5% of all recorded clinical episodes of malaria. Parasite prevalence was recorded as 75% at the start of the study in 1993, falling to 48% in 1998, as measured by microscopy in the 2- to 9-year-old children. A total of 962 individuals with pedigree information were genotyped; of these 278 were DUP4 heterozygotes and 4 were DUP4 homozygotes. Previous work has suggested that the DUP4 variant is at a frequency of about 3% in the Wasambaa of north-eastern Tanzania,5 and our analysis found an allele frequency of 13.4% (95% confidence intervals 11.0%–16.1%) in the 348 unrelated individuals from Nyamisati village. For these unrelated individuals, 87 were DUP4 heterozygotes and 3 were DUP4 homozygotes, with genotype frequencies in Hardy-Weinberg equilibrium. We used the pedigree and genotype information from our full cohort to test for association of three malaria-related phenotypes with the DUP4 variant. Using a family-based association method modeled in QTDT,36 we found a statistically significant association of the DUP4 variant with hemoglobin levels (p = 0.0054, Table 1). We estimated the direction of effect by comparing the mean corrected hemoglobin levels of unrelated individuals with and without the DUP4 variant. Individuals with the DUP4 allele showed a higher hemoglobin level compared to those without a DUP4 variant, showing that DUP4 variant is associated with higher hemoglobin levels.