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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Homozygosity and risk of childhood death due to invasive bacterial disease
BMC Medical Genetics, Volume 10, Article 55, Year 2009
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Description
Background: Genetic heterozygosity is increasingly being shown to be a key predictor of fitness in natural populations, both through inbreeding depression, inbred individuals having low heterozygosity, and also through chance linkage between a marker and a gene under balancing selection. One important component of fitness that is often highlighted is resistance to parasites and other pathogens. However, the significance of equivalent loci in human populations remains unclear. Consequently, we performed a case-control study of fatal invasive bacterial disease in Kenyan children using a genome-wide screen with microsatellite markers. Methods: 148 cases, comprising children aged <13 years who died of invasive bacterial disease, (variously, bacteraemia, bacterial meningitis or neonatal sepsis) and 137 age-matched, healthy children were sampled in a prospective study conducted at Kilifi District Hospital, Kenya. Samples were genotyped for 134 microsatellite markers using the ABI LD20 marker set and analysed for an association between homozygosity and mortality. Results: At five markers homozygosity was strongly associated with mortality (odds ratio range 4.7-12.2) with evidence of interactions between some markers. Mortality was associated with different non-overlapping marker groups in Gram positive and Gram negative bacterial disease. Homozygosity at susceptibility markers was common (prevalence 19-49%) and, with the large effect sizes, this suggests that bacterial disease mortality may be strongly genetically determined. Conclusion: Balanced polymorphisms appear to be more widespread in humans than previously appreciated and play a critical role in modulating susceptibility to infectious disease. The effect sizes we report, coupled with the stochasticity of exposure to pathogens suggests that infection and mortality are far from random due to a strong genetic basis. © 2009 Lyons et al; licensee BioMed Central Ltd.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2714084/bin/1471-2350-10-55-S1.doc
Authors & Co-Authors
Lyons, Emily J.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, London
Imperial College London
Amos, William
United Kingdom, Cambridge
University of Cambridge
Berkley, James A.
Kenya, Kilifi
Centre for Geographic Medicine Research
Mwangi, Isaiah
United Kingdom, Cambridge
University of Cambridge
Shafi, Mohammed J.
Kenya, Kilifi
Centre for Geographic Medicine Research
Williams, Thomas Neil
Kenya, Kilifi
Centre for Geographic Medicine Research
Newton, Charles R.J.C.
Kenya, Kilifi
Centre for Geographic Medicine Research
Peshu, Norbert M.
Kenya, Kilifi
Centre for Geographic Medicine Research
Marsh, Kevin
Kenya, Kilifi
Centre for Geographic Medicine Research
Scott, John Anthony Gerard
Kenya, Kilifi
Centre for Geographic Medicine Research
Hill, Adrian V. S.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Statistics
Citations: 40
Authors: 11
Affiliations: 4
Identifiers
Doi:
10.1186/1471-2350-10-55
Research Areas
Genetics And Genomics
Health System And Policy
Maternal And Child Health
Mental Health
Study Design
Cross Sectional Study
Cohort Study
Case-Control Study
Study Locations
Kenya