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Open Access Highly Accessed Research article

A genome-wide association study of variants associated with acquisition of Staphylococcus aureus bacteremia in a healthcare setting

Charlotte L Nelson1*, Kimberly Pelak2, Mihai V Podgoreanu13, Sun Hee Ahn4, William K Scott5, Andrew S Allen16, Lindsay G Cowell7, Thomas H Rude4, Yurong Zhang4, Amy Tong4, Felicia Ruffin4, Batu K Sharma-Kuinkel4 and Vance G Fowler,14

Author Affiliations

1 Duke Clinical Research Institute, Duke University Medical Center, 2400 Pratt Street, Room 0311 Terrace Level, Durham, NC 27705, USA

2 Center for Human Genome Variation, Duke University School of Medicine, Durham, NC 27708, USA

3 Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA

4 Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA

5 Department of Human Genetics and Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA

6 Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27710, USA

7 UT Southwestern Medical Center, Dallas, TX 75390, USA

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BMC Infectious Diseases 2014, 14:83  doi:10.1186/1471-2334-14-83

Published: 13 February 2014

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.

Keywords:
Genomics; Genome-wide association study; Case–control study; Staphylococcus aureus; Bacteremia; Gram-positive bacterial infections; Polymorphism, single-nucleotide; Infections; Nosocomial; Cross infection