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A genome-wide association study of variants associated with acquisition of Staphylococcus aureus bacteremia in a healthcare setting.
Abstract
BACKGROUND: Humans vary in their susceptibility to acquiring Staphylococcus aureus
infection, and research suggests that there is a genetic basis for this variability.
Several recent genome-wide association studies (GWAS) have identified variants that
may affect susceptibility to infectious diseases, demonstrating the potential value
of GWAS in this arena. METHODS: We conducted a GWAS to identify common variants associated
with acquisition of S. aureus bacteremia (SAB) resulting from healthcare contact.
We performed a logistic regression analysis to compare patients with healthcare contact
who developed SAB (361 cases) to patients with healthcare contact in the same hospital
who did not develop SAB (699 controls), testing 542,410 SNPs and adjusting for age
(by decade), sex, and 6 significant principal components from our EIGENSTRAT analysis.
Additionally, we evaluated the joint effect of the host and pathogen genomes in association
with severity of SAB infection via logistic regression, including an interaction of
host SNP with bacterial genotype, and adjusting for age (by decade), sex, the 6 significant
principal components, and dialysis status. Bonferroni corrections were applied in
both analyses to control for multiple comparisons. RESULTS: Ours is the first study
that has attempted to evaluate the entire human genome for variants potentially involved
in the acquisition or severity of SAB. Although this study identified no common variant
of large effect size to have genome-wide significance for association with either
the risk of acquiring SAB or severity of SAB, the variant (rs2043436) most significantly
associated with severity of infection is located in a biologically plausible candidate
gene (CDON, a member of the immunoglobulin family) and may warrant further study.
CONCLUSIONS: The genetic architecture underlying SAB is likely to be complex. Future
investigations using larger samples, narrowed phenotypes, and advances in both genotyping
and analytical methodologies will be important tools for identifying causative variants
for this common and serious cause of healthcare-associated infection.
Type
Journal articleSubject
AdultAged
Bacteremia
Case-Control Studies
Cross Infection
Female
Genetic Predisposition to Disease
Genome, Human
Genome-Wide Association Study
Genotype
Humans
Logistic Models
Male
Middle Aged
Phenotype
Principal Component Analysis
Risk
Staphylococcal Infections
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https://hdl.handle.net/10161/13316Published Version (Please cite this version)
10.1186/1471-2334-14-83Publication Info
Nelson, Charlotte L; Pelak, Kimberly; Podgoreanu, Mihai V; Ahn, Sun Hee; Scott, William
K; Allen, Andrew S; ... Fowler, Vance G (2014). A genome-wide association study of variants associated with acquisition of Staphylococcus
aureus bacteremia in a healthcare setting. BMC Infect Dis, 14. pp. 83. 10.1186/1471-2334-14-83. Retrieved from https://hdl.handle.net/10161/13316.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Andrew Scott Allen
Professor of Biostatistics & Bioinformatics
My research focuses on developing new statistical methods for identifying susceptibility
loci involved in complex human disease. It involves a mix of genetics, statistics,
and computer science and is motivated by the complexities of real data encountered
in collaborative disease-gene mapping projects.
Vance Garrison Fowler Jr.
Florence McAlister Distinguished Professor of Medicine
Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia Antibacterial
ResistancePathogenesis of Bacterial Infections Tropical medicine/International Health
Mihai V. Podgoreanu
Associate Professor of Anesthesiology
Basic-Translational: 1. Systems biology approaches to modeling perioperative cardiovascular
injury and adaptation. 2. Mechanisms of perioperative myocardial injury; functional
genomics applied to perioperative myocardial injury. 3. Metabolic consequences of
perioperative myocardial ischemia-reperfusion injury. 4. Animal models and comparative
genomic approaches to study perioperative myocardial ischemia-reperfusion injury.
5. Functional genomics of vein graft diseas
Felicia Ruffin
Research Program Leader, Tier 1
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