Volume 83, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Many factors influence variation in 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% ( < 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 ( < 0.001), but there was no genetic involvement in adults. Domestic environment did not explain variation in children and explained 5% in adults ( = 0.09). Genetic effects are an important determinant of parasite density in children in this population, consistent with previous quantitative genetic studies of parasitaemia, although differences in environmental exposure play a lesser role.


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  1. Haldane JB, , 1949. The rate of mutation of human genes. Hereditas 35: 267272.[Crossref] [Google Scholar]
  2. Kwiatkowski DP, , 2005. How malaria has affected the human genome and what human genetics can teach us about malaria. Am J Hum Genet 77: 171192.[Crossref] [Google Scholar]
  3. Williams-Blangero S, Blangero J, , 2006. Collection of pedigree data for genetic analysis in isolate populations. Hum Biol 78: 89101.[Crossref] [Google Scholar]
  4. Jepson AP, Banya WA, Sisay-Joof F, Hassan-King M, Bennett S, Whittle HC, , 1995. Genetic regulation of fever in Plasmodium falciparum malaria in Gambian twin children. J Infect Dis 172: 316319.[Crossref] [Google Scholar]
  5. Ranque S, Safeukui I, Poudiougou B, Traore A, Keita M, Traore D, Diakite M, Cisse MB, Keita MM, Doumbo OK, Dessein AJ, , 2005. Familial aggregation of cerebral malaria and severe malarial anemia. J Infect Dis 191: 799804.[Crossref] [Google Scholar]
  6. Stirnadel HA, Al-Yaman F, Genton B, Alpers MP, Smith TA, , 2000. Assessment of different sources of variation in the antibody responses to specific malaria antigens in children in Papua New Guinea. Int J Epidemiol 29: 579586.[Crossref] [Google Scholar]
  7. Mackinnon MJ, Mwangi TW, Snow RW, Marsh K, Williams TN, , 2005. Heritability of malaria in Africa. PLoS Med 2: e340.[Crossref] [Google Scholar]
  8. Mackinnon MJ, Gunawardena DM, Rajakaruna J, Weerasingha S, Mendis KN, Carter R, , 2000. Quantifying genetic and nongenetic contributions to malarial infection in a Sri Lankan population. Proc Natl Acad Sci USA 97: 1266112666.[Crossref] [Google Scholar]
  9. Phimpraphi W, Paul R, Witoonpanich B, Turbpaiboon C, Peerapittayamongkol C, Louicharoen C, Casademont I, Tungpradabkul S, Krudsood S, Kaewunwal J, Sura T, Looareesuwan S, Singhasivanon P, Sakuntabhai A, , 2008. Heritability of P. falciparum and P. vivax malaria in a Karen population in Thailand. PLoS One 3: e3887.[Crossref] [Google Scholar]
  10. Enevold A, Alifrangis M, Sanchez JJ, Carneiro I, Roper C, Borsting C, Lusingu J, Vestergaard LS, Lemnge MM, Morling N, Riley E, Drakely CJ, , 2007. Associations between alpha+−thalassemia and Plasmodium falciparum malarial infection in northeastern Tanzania. J Infect Dis 196: 451459.[Crossref] [Google Scholar]
  11. Oppenheimer SJ, Higgs DR, Weatherall DJ, Barker J, Spark RA, , 1984. Alpha thalassaemia in Papua New Guinea. Lancet 1: 424426.[Crossref] [Google Scholar]
  12. Cattani JA, Gibson FD, Alpers MP, Crane GG, , 1987. Hereditary ovalocytosis and reduced susceptibility to malaria in Papua New Guinea. Trans R Soc Trop Med Hyg 81: 705709.[Crossref] [Google Scholar]
  13. Parikh S, Dorsey G, Rosenthal PJ, , 2004. Host polymorphisms and the incidence of malaria in Ugandan children. Am J Trop Med Hyg 71: 750753. [Google Scholar]
  14. Tripathy V, Reddy BM, , 2007. Present status of understanding on the G6PD deficiency and natural selection. J Postgrad Med 53: 193202.[Crossref] [Google Scholar]
  15. Aidoo M, Terlouw DJ, Kolczak MS, McElroy PD, ter Kuile FO, Kariuki S, Nahlen BL, Lal AA, Udhayakumar V, , 2002. Protective effects of the sickle cell gene against malaria morbidity and mortality. Lancet 359: 13111312.[Crossref] [Google Scholar]
  16. Wambua S, Mwangi TW, Kortok M, Uyoga SM, Macharia AW, Mwacharo JK, Weatherall DJ, Snow RW, Marsh K, Williams TN, , 2006. The effect of alpha+−thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya. PLoS Med 3: e158.[Crossref] [Google Scholar]
  17. Mockenhaupt FP, Falusi AG, May J, Ademowo OG, Olumese PE, Meyer CG, Bienzle U, , 1999. The contribution of alpha+−thalassaemia to anaemia in a Nigerian population exposed to intense malaria transmission. Trop Med Int Health 4: 302307.[Crossref] [Google Scholar]
  18. Oppenheimer SJ, Hill AV, Gibson FD, Macfarlane SB, Moody JB, Pringle J, , 1987. The interaction of alpha thalassaemia with malaria. Trans R Soc Trop Med Hyg 81: 322326.[Crossref] [Google Scholar]
  19. Bienzle U, Guggenmoos-Holzmann I, Luzzatto L, , 1981. Plasmodium falciparum malaria and human red cells. I. A genetic and clinical study in children. Int J Epidemiol 10: 915.[Crossref] [Google Scholar]
  20. Fowkes FJ, Imrie H, Migot-Nabias F, Michon P, Justice A, Deloron P, Luty AJ, Day KP, , 2006. Association of haptoglobin levels with age, parasite density, and haptoglobin genotype in a malaria-endemic area of Gabon. Am J Trop Med Hyg 74: 2630. [Google Scholar]
  21. Fowkes FJ, Michon P, Pilling L, Ripley RM, Tavul L, Imrie HJ, Woods CM, Mgone CS, Luty AJ, Day KP, , 2008. Host erythrocyte polymorphisms and exposure to Plasmodium falciparum in Papua New Guinea. Malar J 7: 1.[Crossref] [Google Scholar]
  22. Abel L, Cot M, Mulder L, Carnevale P, Feingold J, , 1992. Segregation analysis detects a major gene controlling blood infection levels in human malaria. Am J Hum Genet 50: 13081317. [Google Scholar]
  23. Garcia A, Cot M, Chippaux JP, Ranque S, Feingold J, Demenais F, Abel L, , 1998. Genetic control of blood infection levels in human malaria: evidence for a complex genetic model. Am J Trop Med Hyg 58: 480488. [Google Scholar]
  24. Rihet P, Abel L, Traore Y, Traore-Leroux T, Aucan C, Fumoux F, , 1998. Human malaria: segregation analysis of blood infection levels in a suburban area and a rural area in Burkina Faso. Genet Epidemiol 15: 435450.[Crossref] [Google Scholar]
  25. Garcia A, Marquet S, Bucheton B, Hillaire D, Cot M, Fievet N, Dessein AJ, Abel L, , 1998. Linkage analysis of blood Plasmodium falciparum levels: interest of the 5q31-q33 chromosome region. Am J Trop Med Hyg 58: 705709. [Google Scholar]
  26. Rihet P, Traore Y, Abel L, Aucan C, Traore-Leroux T, Fumoux F, , 1998. Malaria in humans: Plasmodium falciparum blood infection levels are linked to chromosome 5q31-q33. Am J Hum Genet 63: 498505.[Crossref] [Google Scholar]
  27. Flori L, Kumulungui B, Aucan C, Esnault C, Traore AS, Fumoux F, Rihet P, , 2003. Linkage and association between Plasmodium falciparum blood infection levels and chromosome 5q31-q33. Genes Immun 4: 265268.[Crossref] [Google Scholar]
  28. Sakuntabhai A, Ndiaye R, Casademont I, Peerapittayamongkol C, Rogier C, Tortevoye P, Tall A, Paul R, Turbpaiboon C, Phimpraphi W, Trape JF, Spiegel A, Heath S, Mercereau-Puijalon O, Dieye A, Julier C, , 2008. Genetic determination and linkage mapping of Plasmodium falciparum related traits in Senegal. PLoS One 3: e2000.[Crossref] [Google Scholar]
  29. Carpenter D, Rooth I, Farnert A, Abushama H, Quinnell RJ, Shaw MA, , 2009. Genetics of susceptibility to malaria related phenotypes. Infect Genet Evol 9: 97103.[Crossref] [Google Scholar]
  30. Pullan RL, Bukirwa H, Staedke SG, Snow RW, Brooker S, , 2010. Plasmodium infection and its risk factors in eastern Uganda. Malar J 9: 2.[Crossref] [Google Scholar]
  31. Hay SI, Guerra CA, Gething PW, Patil AP, Tatem AJ, Noor AM, Kabaria CW, Manh BH, Elyazar IR, Brooker S, Smith DL, Moyeed RA, Snow RW, , 2009. A world malaria map: Plasmodium falciparum endemicity in 2007. PLoS Med 24: e1000048.[Crossref] [Google Scholar]
  32. Makinen V-P, Parkkonen M, Wessman M, Groop P-H, Kanninen T, Kashi K, , 2005. High-throughput pedigree drawing. Eur J Hum Genet 13: 987989.[Crossref] [Google Scholar]
  33. Almasy L, Blangero J, , 1998. Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 62: 11981211.[Crossref] [Google Scholar]
  34. Khoury MJ, Beaty TH, Cohen BH, , 1993. Fundamentals of Genetic Epidemiology. New York, NY: Oxford University Press. [Google Scholar]
  35. Rice TK, Borecki IB, , 2001. Familial resemblance and heritability. Adv Genet 42: 3544. [Google Scholar]
  36. Towne B, Blangero J, Siervogel RM, , 1993. Genotype by sex interavtion in measures of lipids, lipoproteins, and apolipoproteins. Genet Epidemiol 10: 611616.[Crossref] [Google Scholar]
  37. Breitling LP, Wilson AJ, Raiko A, Lagog M, Siba M, Shaw MA, Quinnell RJ, , 2008. Heritability of human hookworm infection in Papua New Guinea. Parasitology 135: 14071415.[Crossref] [Google Scholar]
  38. Williams TN, , 2006. Human red blood cell polymorphisms and malaria. Curr Opin Microbiol 9: 388394.[Crossref] [Google Scholar]
  39. Burt RA, Baldwin TM, Marshall VM, Foote SJ, , 1999. Temporal expression of an H2-linked locus in host response to mouse malaria. Immunogenetics 50: 278285.[Crossref] [Google Scholar]
  40. Fortin A, Stevenson MM, Gros P, , 2002. Susceptibility to malaria as a complex trait: big pressure from a tiny creature. Hum Mol Genet 20: 24692478.[Crossref] [Google Scholar]
  41. Wahyuni S, Houwing-Duistermaat JJ, Syafruddin D, Supali T, Yazdanbakhsh M, Sartono E, , 2004. Clustering of filarial infection in an age-graded study: genetic, household and environmental influences. Parasitology 128: 315321.[Crossref] [Google Scholar]
  42. Okell LC, Ghani AC, Lyons E, Drakeley C, , 2009. Submicroscopic infection in Plasmodium falciparum endemic populations: a systematic review and meta-analysis. J Infect Dis 15: 15091517.[Crossref] [Google Scholar]
  43. Stirnadel HA, Beck HP, Alpers M, Smith TA, , 2000. Genetic analysis of IgG subclass responses against RESA and MSP2 of Plasmodium falciparum in adults in Papua New Guinea. Epidemiol Infect 124: 153162.[Crossref] [Google Scholar]
  44. Stirnadel HA, Beck HP, Alpers M, Smith TA, , 1999. Heritability and segregation analysis of immune responses to specific malaria antigens in Papua New Guinea. Genet Epidemiol 17: 1634.[Crossref] [Google Scholar]
  45. Duah NO, Weiss HA, Jepson AP, Tetteh KKA, Whittle HC, Conway DJ, , 2009. Heritability of antibody isotype and subclass responses to Plasmodium falciparum antigens. PLoS One 4: e7381.[Crossref] [Google Scholar]
  46. Garcia A, Dieng AB, Rouget F, Migot-Nabias F, Le Hesran JY, Gaye O, , 2004. Role of environment and behaviour in familial resemblances of Plasmodium falciparum infection in a population of Senegalese children. Microbes Infect 6: 6875.[Crossref] [Google Scholar]
  47. Ekstrom CT, , 2009. The impact of pedigree structure on heritability estimates. Hum Hered 68: 243251.[Crossref] [Google Scholar]
  48. Van Vleck LD, , 1970. Misidentification in estimating the paternal-sib correlation. J Dairy Sci 53: 14691474.[Crossref] [Google Scholar]
  49. Bethony J, Williams JT, Blangero J, Kloos H, Gazzinelli A, Soares-Filho B, Coelho L, Alves-Fraga L, Williams-Blangero S, Loverde PT, Correa-Oliveira R, , 2002. Additive host genetic factors influence fecal egg excretion rates during Schistosoma mansoni infection in a rural area in Brazil. Am J Trop Med Hyg 67: 336343. [Google Scholar]
  50. Farnert A, Snounou G, Rooth I, Bjorkman A, , 1997. Daily dynamics of Plasmodium falciparum subpopulations in asymptomatic children in a holoendemic area. Am J Trop Med Hyg 56: 538547. [Google Scholar]
  51. Delley V, Bouvier P, Breslow N, Doumbo O, Sagara I, Diakite M, Mauris A, Dolo A, Rougemont A, , 2000. What does a single determination of malaria parasite density mean? A longitudinal survey in Mali. Trop Med Int Health 5: 404412.[Crossref] [Google Scholar]
  52. Network MGE, , 2008. A global network for investigating the genomic epidemiology of malaria. Nature 456: 732737.[Crossref] [Google Scholar]

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Supplemental appendices

  • Received : 22 Jan 2010
  • Accepted : 15 May 2010
  • Published online : 05 Nov 2010

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