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.
|State||Published - Nov 1 2015|
Bibliographical noteFunding Information:
This work was supported by NIH grants R01 AI085014-01A1 (E.L. Brown and C.L. Hanis), R01 GM104390 (C.D. Huff and H. Hao), HL102830 (C.L. Hanis), DK085501 (C.L. Hanis) and P30DK020595 (G.I. Bell). H. Hao is also supported by the M.D. Anderson Cancer Center Odyssey Program. This work was also partially supported from a grant from the Kleberg Foundation to E.L.B. Genotyping imputation and whole exome sequencing were performed as part of our involvement in the T2D-GENES Consortium and we acknowledge those efforts. We also express appreciation to the field staff in Starr County who contacted and collected the necessary participant data and samples. Lastly, we thank the participants for their generous and willing participation.
© 2015 Brown et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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