Genome-Wide Association Study of Staphylococcus aureus Carriage in a Community-Based Sample of Mexican-Americans in Starr County, Texas.
Genome-Wide Association Study of Staphylococcus aureus Carriage in a Community-Based Sample of Mexican-Americans in Starr County, Texas.
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DOI：
10.1371/journal.pone.0142130
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hanis CL
中科院分区：
文献类型：
--
作者：
Brown EL;Below JE;Fischer RS;Essigmann HT;Hu H;Huff C;Robinson DA;Petty LE;Aguilar D;Bell GI;Hanis CL
金黄色葡萄球菌是医院获得性感染的首要原因。了解宿主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，全外显子组序列和基于芯片的基因型数据用于在德克萨斯州斯塔尔县的墨西哥裔美国人队列中进行罕见变异和全基因组关联分析，以鉴定与S.金黄色鼻疽与S.金黄色葡萄球菌是基于住院人群，这项研究使用了一个代表性的社区样本。在2009年10月至2013年12月期间，从参与者（n = 858）中收集了两份鼻拭子，间隔11-17天，筛查是否存在S。金黄色葡萄球菌，然后分类为持续性，间歇性或非载体。基于芯片和基于外显子序列的单变异关联分析确定了1个间歇性和11个持续性或间歇性S的全基因组显著区域（KAT 2B）。金黄色马车。我们还报告了基于基因的罕见功能变异负担分析的主要结果。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之间的显著差异。在持续携带的单变异分析中，在连续相关区域中的9个基因中的7个和所有5个基于基因的发现与细胞生长或紧密连接完整性相关，或者是细胞骨架的结构成分，这表明与持续携带相关的基因的变异影响细胞的完整性和形态。
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.