Heritability of malaria in Africa
Author(s)
Mackinnon, MJ
Mwangi, TW
Snow, RW
Marsh, K
Williams, TN
Type
Journal Article
Abstract
Background
While many individual genes have been identified that confer protection against malaria, the overall impact of host genetics on malarial risk remains unknown.
Methods and Findings
We have used pedigree-based genetic variance component analysis to determine the relative contributions of genetic and other factors to the variability in incidence of malaria and other infectious diseases in two cohorts of children living on the coast of Kenya. In the first, we monitored the incidence of mild clinical malaria and other febrile diseases through active surveillance of 640 children 10 y old or younger, living in 77 different households for an average of 2.7 y. In the second, we recorded hospital admissions with malaria and other infectious diseases in a birth cohort of 2,914 children for an average of 4.1 y. Mean annual incidence rates for mild and hospital-admitted malaria were 1.6 and 0.054 episodes per person per year, respectively. Twenty-four percent and 25% of the total variation in these outcomes was explained by additively acting host genes, and household explained a further 29% and 14%, respectively. The haemoglobin S gene explained only 2% of the total variation. For nonmalarial infections, additive genetics explained 39% and 13% of the variability in fevers and hospital-admitted infections, while household explained a further 9% and 30%, respectively.
Conclusion
Genetic and unidentified household factors each accounted for around one quarter of the total variability in malaria incidence in our study population. The genetic effect was well beyond that explained by the anticipated effects of the haemoglobinopathies alone, suggesting the existence of many protective genes, each individually resulting in small population effects. While studying these genes may well provide insights into pathogenesis and resistance in human malaria, identifying and tackling the household effects must be the more efficient route to reducing the burden of disease in malaria-endemic areas.
While many individual genes have been identified that confer protection against malaria, the overall impact of host genetics on malarial risk remains unknown.
Methods and Findings
We have used pedigree-based genetic variance component analysis to determine the relative contributions of genetic and other factors to the variability in incidence of malaria and other infectious diseases in two cohorts of children living on the coast of Kenya. In the first, we monitored the incidence of mild clinical malaria and other febrile diseases through active surveillance of 640 children 10 y old or younger, living in 77 different households for an average of 2.7 y. In the second, we recorded hospital admissions with malaria and other infectious diseases in a birth cohort of 2,914 children for an average of 4.1 y. Mean annual incidence rates for mild and hospital-admitted malaria were 1.6 and 0.054 episodes per person per year, respectively. Twenty-four percent and 25% of the total variation in these outcomes was explained by additively acting host genes, and household explained a further 29% and 14%, respectively. The haemoglobin S gene explained only 2% of the total variation. For nonmalarial infections, additive genetics explained 39% and 13% of the variability in fevers and hospital-admitted infections, while household explained a further 9% and 30%, respectively.
Conclusion
Genetic and unidentified household factors each accounted for around one quarter of the total variability in malaria incidence in our study population. The genetic effect was well beyond that explained by the anticipated effects of the haemoglobinopathies alone, suggesting the existence of many protective genes, each individually resulting in small population effects. While studying these genes may well provide insights into pathogenesis and resistance in human malaria, identifying and tackling the household effects must be the more efficient route to reducing the burden of disease in malaria-endemic areas.
Date Issued
2005-11-08
Date Acceptance
2005-08-15
Citation
PLoS Medicine, 2005, 2 (12), pp.1253-1259
ISSN
1549-1277
Publisher
Public Library of Science (PLoS)
Start Page
1253
End Page
1259
Journal / Book Title
PLoS Medicine
Volume
2
Issue
12
Copyright Statement
© 2005 Mackinnon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Identifier
http://www.scopus.com/inward/record.url?eid=2-s2.0-29644447350&partnerID=40&md5=04957dcd6e6258c93d3cdfdf4cbd8bfa
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
PLASMODIUM-FALCIPARUM MALARIA
CHILDREN
SUSCEPTIBILITY
INFECTION
RESPONSES
ANTIGENS
GENETICS
COMPLEX
TRAIT
COAST
Africa
Child
Child, Preschool
Cohort Studies
Female
Genetic Predisposition to Disease
Hemoglobin, Sickle
Humans
Incidence
Kenya
Malaria
Male
Patient Admission
Pedigree
Sri Lanka
alpha-Thalassemia
Humans
Malaria
alpha-Thalassemia
Genetic Predisposition to Disease
Hemoglobin, Sickle
Patient Admission
Incidence
Cohort Studies
Pedigree
Child
Child, Preschool
Africa
Kenya
Sri Lanka
Female
Male
General & Internal Medicine
11 Medical and Health Sciences
Notes
Cited By :102 Export Date: 21 April 2015
Date Publish Online
2005-11-08