Epigenome-wide association study of asthma in populations of African descent

描述（由申请人提供）：哮喘是一种常见的气道慢性炎症性疾病，遗传因素和环境暴露之间的相互作用控制着疾病的易感性和进展。目前，哮喘的流行对美国代表性不足的少数民族造成了不成比例的影响，并造成了重大的公共卫生负担。与非非洲裔患者相比，非洲裔哮喘患者的免疫球蛋白E （IgE）水平往往更高，临床症状也更严重。尽管我们对遗传和环境对哮喘的影响、疾病病因学的分子基础以及遗传和环境因素之间的相互作用的理解取得了很大进展，但对人群中疾病患病率和严重程度差异背后的原因仍然知之甚少。最近对患者的候选基因研究表明，哮喘严重程度与DNA甲基化之间存在显著关联。迫切需要对哮喘进行全面的全基因组甲基化关联研究，以发现哮喘与DNA甲基化之间的新关联。在本应用中，我们建议使用新开发的具有成本效益的基于阵列的技术对居住在北美的非洲裔哮喘患者进行全基因组甲基化分析研究。这些样本是nhlbi支持的美洲非洲裔人群哮喘联盟（CAAPA）队列的一部分，其整个基因型谱已通过全基因组深度测序获得。通过将这里生成的甲基化数据与现有的全基因组测序数据相结合，我们将有独特的机会对这些样本进行全表观基因组关联研究（EWAS）和甲基化QTL分析（meQTL）。我们认为，这项研究的成功完成将有助于我们更好地了解哮喘的病因，以及为什么这种疾病在非洲裔患者中更为严重。

DESCRIPTION (provided by applicant): Asthma is a common chronic inflammatory disease of the airways in which the interplay between genetic factors and environmental exposures controls disease susceptibility and progression. Currently there is an epidemic of asthma that disproportionately affects underrepresented minorities in the US and creates a major public health burden. Asthmatics of African descent tend to have higher Immunoglobulin E (IgE) levels and more severe clinical symptoms than their non-African counterparts. Despite the fact that much progress has been made in our understanding of genetic and environmental influence on asthma, the molecular underpinnings of the disease etiology, and the interactions between genetic and environmental factors, the reasons behind the differences in disease prevalence and severity among populations remain poorly understood. Recent candidate gene studies on patients have demonstrated significant associations between asthma severity and DNA methylation. A comprehensive genome-wide methylation association study on asthma is sorely needed to detect novel associations between asthma and DNA methylation. In this application, we propose to use newly-developed and cost-effective array-based technology to conduct a genome-wide methylation profiling study on Asthma patients of African descent residing in North America. These samples are part of the NHLBI-supported Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) cohort whose entire genotype profile has been obtained using whole genome deep sequencing. By combining methylation data to be generated here with existing whole-genome sequencing data, we will have the unique opportunity to conduct both epigenome-wide association study (EWAS) and methylation QTL analysis (meQTL) on these samples. We believe that the successful completion of the proposed study will help us to better understand the disease etiology of asthma, and why the disease is more severe in patients of African descent.