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Heritability of Plasmodium Parasite Density in a Rural Ugandan Community

Rachel L. PullanDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; Uganda Malaria Surveillance Project, Mulago Hospital, Kampala, Uganda; Malaria Public Health and Epidemiology Group, Kenya Medical Research Institute/Wellcome Trust Research Programme, Nairobi, Kenya; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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Hasifa BukirwaDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; Uganda Malaria Surveillance Project, Mulago Hospital, Kampala, Uganda; Malaria Public Health and Epidemiology Group, Kenya Medical Research Institute/Wellcome Trust Research Programme, Nairobi, Kenya; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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Robert W. SnowDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; Uganda Malaria Surveillance Project, Mulago Hospital, Kampala, Uganda; Malaria Public Health and Epidemiology Group, Kenya Medical Research Institute/Wellcome Trust Research Programme, Nairobi, Kenya; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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Simon BrookerDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; Uganda Malaria Surveillance Project, Mulago Hospital, Kampala, Uganda; Malaria Public Health and Epidemiology Group, Kenya Medical Research Institute/Wellcome Trust Research Programme, Nairobi, Kenya; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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Many factors influence variation in Plasmodium infection levels, including parasite/host genetics, immunity, and exposure. Here, we examine the roles of host genetics and exposure in determining parasite density, and test whether effects differ with age. Data for 1,711 residents of an eastern Ugandan community were used in pedigree-based variance component analysis. Heritability of parasite density was 13% (P < 0.001) but was not significant after controlling for shared household. Allowing variance components to vary between children (< 16 years) and adults (≥ 16 years) revealed striking age differences; 26% of variation could be explained by additively acting genes in children (P < 0.001), but there was no genetic involvement in adults. Domestic environment did not explain variation in children and explained 5% in adults (P = 0.09). Genetic effects are an important determinant of parasite density in children in this population, consistent with previous quantitative genetic studies of Plasmodium parasitaemia, although differences in environmental exposure play a lesser role.

Author Notes

*Address correspondence to Rachel L. Pullan, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1B 3DP, UK. E-mail: rachel.pullan@lshtm.ac.uk

Financial support: R.L.P. is supported by a Medical Research Council Doctoral Training Account (DTA)-funded studentship, R.W.S. is a Wellcome Trust Principal Research Fellow (#079080), and S.B. is supported by a Research Career Development Fellowship from the Wellcome Trust (#081673). The fieldwork was supported through the fellowship for S.B.

Authors' addresses: Rachel L. Pullan, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK, E-mail: rachel.pullan@lshtm.ac.uk. Hasifa Bukirwar, Uganda Malaria Surveillance Project, Mulago Hospital, Kampala, Uganda. Robert W. Snow and Simon Brooker, Malaria Public Health and Epidemiology Group, Kenya Medical Research Institute/Wellcome Trust Research Programme, Nairobi, Kenya.

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