Abstract
Staphylococcus aureus is the number one cause of hospital-acquired infections. Understanding host pathogen interactions is paramount to the development of more effective treatment and prevention strategies. Therefore, whole exome sequence and chip-based genotype data were used to conduct rare variant and genome-wide association analyses in a Mexican-American cohort from Starr County, Texas to identify genes and variants associated with S. aureus nasal carriage. Unlike most studies of S. aureus that are based on hospitalized populations, this study used a representative community sample. Two nasal swabs were collected from participants (n = 858) 11–17 days apart between October 2009 and December 2013, screened for the presence of S. aureus, and then classified as either persistent, intermittent, or non-carriers. The chip-based and exome sequence-based single variant association analyses identified 1 genome-wide significant region (KAT2B) for intermittent and 11 regions suggestively associated with persistent or intermittent S. aureus carriage. We also report top findings from gene-based burden analyses of rare functional variation. Notably, we observed marked differences between signals associated with persistent and intermittent carriage. In single variant analyses of persistent carriage, 7 of 9 genes in suggestively associated regions and all 5 top gene-based findings are associated with cell growth or tight junction integrity or are structural constituents of the cytoskeleton, suggesting that variation in genes associated with persistent carriage impact cellular integrity and morphology.
Highlights
Infectious diseases result from complex interactions between the microorganism, the host, and the environment
Participants testing positive for S. aureus on 2 separate occasions were defined as persistent carriers (n = 141), participants testing positive once were defined as intermittent carriers (n = 97), and participants testing negative on both occasions were defined as non-carriers (n = 620) as previously described [38, 39]
We found genome-wide significance at 1 gene region and 11 other regions meeting suggestive levels of significance for association with persistent and intermittent carriage states by single variant analysis
Summary
Infectious diseases result from complex interactions between the microorganism, the host, and the environment. The first evidence that genetic factors could impact infectious disease outcomes was derived from epidemiological studies that identified differences between human populations exposed to the same infectious organism [9]. This is true for S. aureus [10,11,12], but this pathogen represents a special case because it is an opportunistic pathogen that can colonize humans without causing overt disease [13]. Susceptibility to infectious agents does not typically follow a simple Mendelian pattern of inheritance, largely due to the fact that human immune responses are controlled by complex genetic mechanisms and modifying environmental influences [25, 26]
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