Brown Eric L, Below Jennifer E, Fischer Rebecca S B, Essigmann Heather T, Hu Hao, Huff Chad, Robinson D Ashley, Petty Lauren E, Aguilar David, Bell Graeme I, Hanis Craig L
Center for Infectious Disease, Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center, Houston, TX, United States of America.
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.
PLoS One. 2015 Nov 16;10(11):e0142130. doi: 10.1371/journal.pone.0142130. eCollection 2015.
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.
金黄色葡萄球菌是医院获得性感染的首要原因。了解宿主与病原体的相互作用对于制定更有效的治疗和预防策略至关重要。因此，利用全外显子组序列和基于芯片的基因型数据，对来自得克萨斯州斯塔尔县的墨西哥裔美国人队列进行罕见变异和全基因组关联分析，以确定与金黄色葡萄球菌鼻腔携带相关的基因和变异。与大多数基于住院人群的金黄色葡萄球菌研究不同，本研究使用了具有代表性的社区样本。在2009年10月至2013年12月期间，从参与者（n = 858）身上间隔11 - 17天采集两份鼻拭子，检测金黄色葡萄球菌的存在，然后将其分类为持续携带者、间歇性携带者或非携带者。基于芯片和外显子组序列的单变异关联分析确定了1个全基因组显著区域（KAT2B）与间歇性携带相关，以及11个区域与持续性或间歇性金黄色葡萄球菌携带存在暗示性关联。我们还报告了基于基因的罕见功能变异负担分析的主要发现。值得注意的是，我们观察到与持续性和间歇性携带相关的信号存在显著差异。在持续性携带的单变异分析中，暗示性关联区域的9个基因中有7个以及所有5个基于基因的顶级发现都与细胞生长、紧密连接完整性或细胞骨架的结构成分相关，这表明与持续性携带相关的基因变异会影响细胞完整性和形态。
