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

Publication ,  Journal Article
Nelson, CL; Pelak, K; Podgoreanu, MV; Ahn, SH; Scott, WK; Allen, AS; Cowell, LG; Rude, TH; Zhang, Y; Tong, A; Ruffin, F; Sharma-Kuinkel, BK ...
Published in: BMC Infect Dis
February 13, 2014

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.

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Published In

BMC Infect Dis

DOI

EISSN

1471-2334

Publication Date

February 13, 2014

Volume

14

Start / End Page

83

Location

England

Related Subject Headings

  • Staphylococcal Infections
  • Risk
  • Principal Component Analysis
  • Phenotype
  • Middle Aged
  • Microbiology
  • Male
  • Logistic Models
  • Humans
  • Genotype
 

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Nelson, C. L., Pelak, K., Podgoreanu, M. V., Ahn, S. H., Scott, W. K., Allen, A. S., … Fowler, V. G. (2014). A genome-wide association study of variants associated with acquisition of Staphylococcus aureus bacteremia in a healthcare setting. BMC Infect Dis, 14, 83. https://doi.org/10.1186/1471-2334-14-83
Nelson, Charlotte L., Kimberly Pelak, Mihai V. Podgoreanu, Sun Hee Ahn, William K. Scott, Andrew S. Allen, Lindsay G. Cowell, et al. “A genome-wide association study of variants associated with acquisition of Staphylococcus aureus bacteremia in a healthcare setting.BMC Infect Dis 14 (February 13, 2014): 83. https://doi.org/10.1186/1471-2334-14-83.
Nelson CL, Pelak K, Podgoreanu MV, Ahn SH, Scott WK, Allen AS, et al. A genome-wide association study of variants associated with acquisition of Staphylococcus aureus bacteremia in a healthcare setting. BMC Infect Dis. 2014 Feb 13;14:83.
Nelson, Charlotte L., et al. “A genome-wide association study of variants associated with acquisition of Staphylococcus aureus bacteremia in a healthcare setting.BMC Infect Dis, vol. 14, Feb. 2014, p. 83. Pubmed, doi:10.1186/1471-2334-14-83.
Nelson CL, Pelak K, Podgoreanu MV, Ahn SH, Scott WK, Allen AS, Cowell LG, Rude TH, Zhang Y, Tong A, Ruffin F, Sharma-Kuinkel BK, Fowler VG. A genome-wide association study of variants associated with acquisition of Staphylococcus aureus bacteremia in a healthcare setting. BMC Infect Dis. 2014 Feb 13;14:83.
Journal cover image

Published In

BMC Infect Dis

DOI

EISSN

1471-2334

Publication Date

February 13, 2014

Volume

14

Start / End Page

83

Location

England

Related Subject Headings

  • Staphylococcal Infections
  • Risk
  • Principal Component Analysis
  • Phenotype
  • Middle Aged
  • Microbiology
  • Male
  • Logistic Models
  • Humans
  • Genotype