TY - JOUR
T1 - A genome-wide association study of variants associated with acquisition of Staphylococcus aureus bacteremia in a healthcare setting
AU - Nelson, Charlotte L.
AU - Pelak, Kimberly
AU - Podgoreanu, Mihai V.
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
AU - Sharma-Kuinkel, Batu K.
AU - Fowler, Vance G.
N1 - Funding Information:
VGF served as Chair of V710 Scientific Advisory Committee (Merck); has received grant support from Merck, Cerexa, Pfizer, Novartis, Advanced Liquid Logics, MedImmune, and the National Institutes of Health; has been a paid consultant for Merck, Astellas, Cubist, Cerexa, Durata, Pfizer, NovaDigm, Novartis, Medicines Company, Biosynexus, MedImmune, Galderma, and Inimex; and has received honoraria from Merck, Astellas, Cubist, Pfizer, Theravance, and Novartis. No other authors have any commercial or other association that might pose a conflict of interest.
PY - 2014/2/13
Y1 - 2014/2/13
N2 - 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.
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.
KW - Bacteremia
KW - Case-control study
KW - Cross infection
KW - Genome-wide association study
KW - Genomics
KW - Gram-positive bacterial infections
KW - Infections
KW - Nosocomial
KW - Polymorphism, single-nucleotide
KW - Staphylococcus aureus
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U2 - 10.1186/1471-2334-14-83
DO - 10.1186/1471-2334-14-83
M3 - Article
C2 - 24524581
AN - SCOPUS:84893688185
SN - 1471-2334
VL - 14
JO - BMC Infectious Diseases
JF - BMC Infectious Diseases
IS - 1
M1 - 83
ER -