ArticleBMC medical genetics2009
Homozygosity and risk of childhood death due to invasive bacterial disease.
Article in BMC medical genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Heterozygosity at neutral and immune loci is not associated with neonatal mortality due to microbial infection in Antarctic fur seals.Ecology and evolution · 2019Article
- Weighted likelihood inference of genomic autozygosity patterns in dense genotype data.BMC genomics · 2017Article
- Population-genetic influences on genomic estimates of the inbreeding coefficient: a global perspective.Human heredity · 2014Article
- Genetic susceptibility to infectious disease in East African Shorthorn Zebu: a genome-wide analysis of the effect of heterozygosity and exotic introgression.BMC evolutionary biology · 2013Article
- Genetic analysis of scattered populations of the Indian eri silkworm, Samia cynthia ricini Donovan: Differentiation of subpopulations.Genetics and molecular biology · 2011Article
- Using human demographic history to infer natural selection reveals contrasting patterns on different families of immune genes.Proceedings. Biological sciences · 2011Article
- Candidate genes versus genome-wide associations: which are better for detecting genetic susceptibility to infectious disease?Proceedings. Biological sciences · 2011Article
- A preliminary study of genetic factors that influence susceptibility to bovine tuberculosis in the British cattle herd.PloS one · 2011Article
- The emergence of human-evolutionary medical genomics.Evolutionary applications · 2011Article
- Genetic variability and viral seroconversion in an outcrossing vertebrate population.Proceedings. Biological sciences · 2011Article
- Equine clinical genomics: A clinician's primer.Equine veterinary journal · 2010Review
- Administration of capsule-selective endosialidase E minimizes upregulation of organ gene expression induced by experimental systemic infection with Escherichia coli K1.Microbiology (Reading, England) · 2010Article
- Has human evolution stopped?Rambam Maimonides medical journal · 2010Article
- Consanguinity and increased risk for schizophrenia in Egypt.Schizophrenia research · 2010Article
- Pathophysiology and treatment of septic shock in neonates.Clinics in perinatology · 2010Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
backgroundGenetic 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.
methods148 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.
resultsAt 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.
conclusionBalanced 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.
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