February 24, 2014 – The DCRI’s Vance Fowler, MD, MHS, was senior author of the first genome-wide association study of variants involves in S. aureus acquisition and severity.
In the first study to evaluate the entire human genome for variants in the acquisition or severity of Staphylococcus aureus (S. aureus) infection, DCRI researchers determined that susceptibility to the infection varies widely among individuals.
The study, conducted by the DCRI’s Charlotte Nelson; Mihai V Podgoreanu, MD; Andrew Allen, PhD; Vance Fowler, MD, MHS; and colleagues from Duke and other institutions, appears in the online version of the journal BMC Infectious Diseases.
S. aureus is a bacterium that is found in many people, although only a few develop infections. The cause and severity of these infections are complex and influenced by several factors, including the genetic factors of the host. However, researchers have made limited progress in identifying the specific genes responsible for controlling the acquisition and severity of S. aureus infection. In this study, the researchers attempted to locate these genes by conducting a genome-wide association study of a large cohort of patients with healthcare-associated S. aureus bacteremia (SAB) and a set of controls without SAB in the same hospital. The researchers also sought to evaluate the effect of potential interaction of the host and S. aureus genomes on the severity of clinical outcome.
The researchers performed a logistic regression analysis to compare the SAB cohort (361 cases) with the patients who did not develop SAB (699 controls), testing 542,410 single-nucleotide polymorphisms (SNPs) while adjusting for age, sex, and other factors. They also evaluated the joint effect of the host and pathogen genomes in association with severity of SAB infection.
Although the researchers were unable to locate an SNP with genome-wide significance for association with either the risk of acquiring SAB or severity of SAB, they found that one variant most significantly associated with severity of infection is located in a biologically plausible candidate gene. Further study is needed, they concluded.