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

Charlotte L. Nelson, Kimberly Pelak, Mihai V. Podgoreanu, Sun H. Ahn, William K. Scott, Andrew S. Allen, Lindsay G. Cowell, Thomas H. Rude, Yurong Zhang, Amy Tong, Felicia Ruffin, Batu K. Sharma-Kuinkel, Vance G. Fowler

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Article number83
JournalBMC Infectious Diseases
Volume14
Issue number1
DOIs
StatePublished - Feb 13 2014

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Genome-Wide Association Study
Bacteremia
Staphylococcus aureus
Delivery of Health Care
Single Nucleotide Polymorphism
Infection
Logistic Models
Genome
Human Genome
Cross Infection
Communicable Diseases
Immunoglobulins
Dialysis
Genotype
Regression Analysis
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Infectious Diseases
  • Medicine(all)

Cite this

A genome-wide association study of variants associated with acquisition of Staphylococcus aureus bacteremia in a healthcare setting. / Nelson, Charlotte L.; Pelak, Kimberly; Podgoreanu, Mihai V.; Ahn, Sun H.; Scott, William K.; Allen, Andrew S.; Cowell, Lindsay G.; Rude, Thomas H.; Zhang, Yurong; Tong, Amy; Ruffin, Felicia; Sharma-Kuinkel, Batu K.; Fowler, Vance G.

In: BMC Infectious Diseases, Vol. 14, No. 1, 83, 13.02.2014.

Research output: Contribution to journalArticle

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 2014, 'A genome-wide association study of variants associated with acquisition of Staphylococcus aureus bacteremia in a healthcare setting', BMC Infectious Diseases, vol. 14, no. 1, 83. https://doi.org/10.1186/1471-2334-14-83
Nelson, Charlotte L. ; Pelak, Kimberly ; Podgoreanu, Mihai V. ; Ahn, Sun H. ; Scott, William K. ; Allen, Andrew S. ; Cowell, Lindsay G. ; Rude, Thomas H. ; Zhang, Yurong ; Tong, Amy ; Ruffin, Felicia ; Sharma-Kuinkel, Batu K. ; Fowler, Vance G. / A genome-wide association study of variants associated with acquisition of Staphylococcus aureus bacteremia in a healthcare setting. In: BMC Infectious Diseases. 2014 ; Vol. 14, No. 1.
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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.",
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AU - Ahn, Sun H.

AU - Scott, William K.

AU - Allen, Andrew S.

AU - Cowell, Lindsay G.

AU - Rude, Thomas H.

AU - Zhang, Yurong

AU - Tong, Amy

AU - Ruffin, Felicia

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AB - 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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KW - Gram-positive bacterial infections

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KW - Polymorphism, single-nucleotide

KW - Staphylococcus aureus

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