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Novel genetic risk factors for asthma in African American children: Precision Medicine and the SAGE II Study

机译:非洲裔美国儿童哮喘的新型遗传危险因素:精准医学和SAGE II研究

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摘要

Asthma, an inflammatory disorder of the airways, is the most common chronic disease of children worldwide. There are significant racial/ethnic disparities in asthma prevalence, morbidity, and mortality among US children. This trend is mirrored in obesity, which may share genetic and environmental risk factors with asthma. The majority of asthma biomedical research has been performed in populations of European decent. We sought to identify genetic risk factors for asthma in African American children. We also assessed the generalizability of genetic variants associated with asthma in European and Asian populations to African American children. Our study population consisted of 1227 (812 asthma cases, 415 controls) African American children with genome-wide single nucleotide polymorphism (SNP) data. Logistic regression was used to identify associations between SNP genotype and asthma status. We identified a novel variant in the PTCHD3 gene that is significantly associated with asthma (rs660498, p = 2.2 x 10(-7)) independent of obesity status. Approximately 5 % of previously reported asthma genetic associations identified in European populations replicated in African Americans. Our identification of novel variants associated with asthma in African American children, coupled with our inability to replicate the majority of findings reported in European Americans, underscores the necessity for including diverse populations in biomedical studies of asthma.
机译:哮喘是一种气道炎性疾病,是全世界儿童最常见的慢性疾病。在美国儿童中,哮喘患病率,发病率和死亡率存在明显的种族/种族差异。肥胖反映了这一趋势,肥胖可能与哮喘共享遗传和环境危险因素。大部分哮喘生物医学研究已在欧洲体面的人群中进行。我们试图确定非洲裔美国儿童哮喘的遗传危险因素。我们还评估了欧洲和亚洲人群中与哮喘有关的遗传变异对非裔美国儿童的普遍性。我们的研究人群包括1227名(812例哮喘病例,415例对照)非洲裔美国儿童,这些儿童具有全基因组范围的单核苷酸多态性(SNP)数据。 Logistic回归用于确定SNP基因型与哮喘状态之间的关联。我们在PTCHD3基因中发现了一个新变体,该变体与哮喘显着相关(rs660498,p = 2.2 x 10(-7)),与肥胖状况无关。在欧洲人群中发现的先前报道的哮喘遗传关联中约有5%在非裔美国人中重复。我们在非裔美国人儿童中发现了与哮喘有关的新型变异,再加上我们无法复制在欧洲裔美国人中报告的大多数发现,这凸显了将多样化人群纳入哮喘生物医学研究的必要性。

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