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首页> 外文期刊>BMC Medical Genomics >African ancestry is associated with cluster-based childhood asthma subphenotypes
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African ancestry is associated with cluster-based childhood asthma subphenotypes

机译：非洲血统与基于簇的儿童哮喘亚型有关

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Childhood asthma is a syndrome composed of heterogeneous phenotypes; furthermore, intrinsic biologic variation among racial/ethnic populations suggests possible genetic ancestry variation in childhood asthma. The objective of the study is to identify clinically homogeneous asthma subphenotypes in a diverse sample of asthmatic children and to assess subphenotype-specific genetic ancestry in African-American asthmatic children. A total of 1211 asthmatic children including 813 in the Childhood Asthma Management Program and 398 in the Childhood Asthma Research and Education program were studied. Unsupervised cluster analysis on clinical phenotypes was conducted to identify homogeneous subphenotypes. Subphenotype-specific genetic ancestry was estimated for 167 African-American asthmatic children. Genetic ancestry association with subphenotypes/clinical phenotypes were determined. Three distinct subphenotypes were identified: a moderate atopic dermatitis (AD) group with negative skin prick test (SPT) and preserved lung function; a high AD group with positive SPT and airway hyperresponsiveness; and a low AD group with positive SPT and lower lung function. African ancestry at asthma genome-wide association study (GWAS) SNPs differed between subphenotypes (64, 89, and 94% for the three subphenotypes, respectively) and was inversely correlated with AD; each additional 10% increase in African ancestry was associated with 1.5 fold higher in IgE and 6.3 higher odds of positive SPT (all p-values
机译：儿童哮喘是一种由异型表型组成的综合征。此外，种族/族裔人群之间的内在生物学差异表明，儿童哮喘可能存在遗传起源变异。该研究的目的是在各种哮喘儿童中鉴定临床上均一的哮喘亚型，并评估非裔美国哮喘儿童中亚表型特异性遗传。总共对1211名哮喘儿童进行了研究，其中包括“儿童哮喘管理计划”中的813名儿童和“儿童哮喘研究与教育”计划中的398名。对临床表型进行无监督聚类分析以鉴定同质亚表型。估计了167名非裔美国哮喘儿童的亚表型特异性遗传血统。确定了遗传血统与亚表型/临床表型的关联。确定了三种不同的亚表型：中度特应性皮炎（AD）组，皮肤点刺试验（SPT）阴性，肺功能得以保留;高AD人群，SPT阳性，气道反应过度;低AD组，SPT阳性，肺功能降低。非洲血统在哮喘全基因组关联研究（GWAS）中的SNP在亚表型之间有所不同（三种亚表型分别为64％，89％和94％），并且与AD呈负相关。非洲血统每增加10％，IgE升高1.5倍，SPT阳性的几率升高6.3（所有p值<0.0001）。通过进行基于表型的聚类分析并评估亚表型特定的遗传谱系，我们能够确定儿童哮喘的同质亚表型，这些表型在非裔美国哮喘儿童的遗传谱系中显示出显着差异。这一发现证明了这些互补方法在理解和改善儿童哮喘亚表型以及实现更有针对性的治疗中的实用性。

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