title: Genome-Wide Association Study of Staphylococcus aureus Carriage in a Community-Based Sample of Mexican-Americans in Starr County, Texas.
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.
authors.affiliation: Center for Infectious Disease, Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center, Houston, TX, United States of America.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Brown
authors.affiliation: Human Genetics Center, Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX, United States of America.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Below
authors.affiliation: Center for Infectious Disease, Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center, Houston, TX, United States of America.
authors.forename: Rebecca S B
authors.initials: RS
authors.lastname: Fischer
authors.affiliation: Center for Infectious Disease, Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center, Houston, TX, United States of America.
authors.forename: Heather T
authors.initials: HT
authors.lastname: Essigmann
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Chad
authors.initials: C
authors.lastname: Huff
authors.affiliation: Department of Microbiology, University of Mississippi Medical Center, Jackson, MS, United States of America.
authors.forename: D Ashley
authors.initials: DA
authors.lastname: Robinson
authors.affiliation: Human Genetics Center, Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX, United States of America.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Petty
authors.affiliation: Winters Center for Heart Failure Research and Section of Cardiology, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Aguilar
authors.affiliation: Departments of Medicine and Human Genetics, The University of Chicago, Chicago, United States of America.
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Bell
authors.affiliation: Human Genetics Center, Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX, United States of America.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Hanis
mesh_terms: D000328:Adult; D000368:Aged; D002353:Carrier State; D015331:Cohort Studies; D059472:Exome; D005091:Exons; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007249:Inflammation; D008297:Male; D017058:Mexican Americans; D008875:Middle Aged; D009666:Nose / Q000382:microbiology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D013203:Staphylococcal Infections / Q000208:ethnology / Q000235:genetics*; D013211:Staphylococcus aureus; D013781:Texas; D050880:p300-CBP Transcription Factors / Q000235:genetics; D000099224:p300-CBP-Associated Factor
chemical_list: D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor