Heritability of P. falciparum and P. vivax malaria in a Karen population in Thailand

Abstract

The majority of studies concerning malaria host genetics have focused on individual genes that confer protection against rather than susceptibility to malaria. Establishing the relative impact of genetic versus non-genetic factors on malaria infection and disease is essential to focus effort on key determinant factors. This relative contribution has rarely been evaluated for Plasmodium falciparum and almost never for Plasmodium vivax. We conducted a longitudinal cohort study in a Karen population of 3,484 individuals in a region of mesoendemic malaria, Thailand from 1998 to 2005. The number of P. falciparum and P. vivax clinical cases and the parasite density per person were determined. Statistical analyses were performed to account for the influence of environmental factors and the genetic heritability of the phenotypes was calculated using the pedigree-based variance components model. The genetic contribution to the number of clinical episodes resulting from P. falciparum and P. vivax were 10% and 19% respectively. There was also moderate genetic contribution to the maximum and overall parasite trophozoite density phenotypes for both P. falciparum (16%&16%) and P. vivax (15%&13%). These values, for P. falciparum, were similar to those previously observed in a region of much higher transmission intensity in Senegal, West Africa. Although environmental factors play an important role in acquiring an infection, genetics plays a determinant role in the outcome of an infection with either malaria parasite species prior to the development of immunity.

Figure 1. Proportions of variation explained by genetic heritability, house and environmental factors found to have a significant effect on the phenotype measured (Table 3&6).

(A) Number of clinical episodes of P. falciparum (PFA); (B) Number of clinical episodes of P. vivax (PVA); (C) Number of non-malaria clinical episodes (NMF); (D) Maximum P. falciparum parasite density (mx-PFD); (E) Overall P. falciparum parasite density (PFD); (F) Maximum P. vivax parasite density (mx-PVD); (G) Overall P. vivax parasite density (PVD). Values of 1% or less not indicated numerically in the figure.