Post Genome-Wide Association Study of Food Allergy

食物过敏后全基因组关联研究

• 批准号: 8689888
• 负责人: XIAOBIN WANG
• 金额: $ 39.31万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8689888
• 关键词: Address; African American; Age; Allergic; Allergic Disease; Biological; Boston; Caucasians; Caucasoid Race; Characteristics; Chicago; Child; Clinical; Cohort Studies; Complex; Copy Number Polymorphism; Data; Data Collection; Enrollment; Epidemiologic Studies; Ethnic Origin; Etiology; Family; Food Hypersensitivity; Future; Gender; Genes; Genetic; Genotype; Hispanics; Joints; Maps; Molecular Genetics; Parents; Phenotype; Population; Prevention strategy; Protocols documentation; Public Health; Publishing; Recording of previous events; Records; Resources; Role; Sampling; Testing; Variant; base; case control; cohort; cost; design; genetic association; genetic variant; genome wide association study; genome-wide; novel; prevent; public health relevance; success; trait

DESCRIPTION (provided by applicant): Food allergy (FA) is a growing clinical and public health problem in the U.S. and worldwide. The major obstacle in preventing and treating FA has been our incomplete understanding of its etiology and biological mechanisms. FA is believed to be a complex trait and determined by multiple environmental and genetic factors. A positive family history is a well-recognized predictor of allergic diseases. Our published and preliminary data underscore the important roles of genetic factors in FA. This proposal is a natural extension of our ongoing genome-wide association study (GWAS) of FA, which includes 1,000 Caucasian FA case-parents trios from Chicago. Genotyping was performed using the lllumina HumanOmni1-Quad BeadChip. Preliminary results from the GWAS are encouraging. This proposal will accomplish the following aims by utilizing two large, well-phenotyped study cohorts enrolled in Chicago and Boston, which were designed for large-scale molecular genetic epidemiologic studies of FA using a standard data collection protocol. Aim 1A. Confirmation study in an independent Caucasian sample: We plan to genotype promising SNPs/copy number variations (CNVs) identified from the GWAS and perform joint analysis in an independent sample of 1,200 Caucasian children using a case-control design: 600 Caucasian FA cases and 600 matched non-allergic controls from Chicago. Aim IB. Replication Study in a Multiethnic Sample: For those SNPs/CNVs that have reached genome-wide significance (p<10-7) in the joint analysis from 1A, we plan to further genotype and test genetic association in an independent sample (n=1,800) using a nested case-control design: 600 FA cases and 1,200 matched non-allergic controls identified from the Boston Cohort. Of those, two thirds are African Americans and one third are Caucasians/Hispanics. Aim 2. Fine Mapping to Search for Causative Variants: Based on the findings in Aim 1A and 1B, we will proceed to the discovery of novel SNPs/CNVs in the promising regions, by focused genotyping and association testing in the combined samples (n=6000 subjects), including the 1,000 FA trios and 600 FA case-control pairs from Chicago (n=4200) and 600 FA cases and 1200 controls from Boston (n=1800). This proposed study will be the first large-scale Post GWAS of FA in multi-ethnic U.S. populations. It has a high likelihood of success given the strong preliminary data, unique resources, and the team's track records. Findings from this study may transform our understanding of the causes of FA and inform future studies.

描述（由申请人提供）：食物过敏（FA）是美国和全球范围内日益增长的临床和公共卫生问题。防止和治疗FA的主要障碍是我们对其病因和生物学机制的不完全理解。 FA被认为是一个复杂的性状，由多个环境和遗传因素决定。积极的家族史是过敏性疾病的公认预测指标。我们发表的和初步的数据强调了遗传因素在FA中的重要作用。该提案是我们正在进行的全基因组协会研究（GWAS）的自然扩展，其中包括来自芝加哥的1,000名高加索FA病例 - 父母三重奏。使用lllumina hymomni1-Quad Beadchip进行基因分型。 GWAS的初步结果令人鼓舞。该提案将通过利用在芝加哥和波士顿招收的两项大型，良好的研究队列来实现以下目的，这些研究群是使用标准数据收集方案设计用于FA的大型分子遗传流行病学研究的。目标1a。在独立的高加索样本中的确认研究：我们计划在GWAS中鉴定出的基因型有希望的SNP/拷贝数变化（CNV），并在使用案例对照的1,200名白种儿童的独立样本中进行了联合分析：使用案例对照组设计：600多首高加索FA案例和600个匹配的非抗抗病控制。目标IB。在一个多种族样本中的复制研究：对于从1A的联合分析中达到了全基因组显着性（P <10-7）的SNP/CNV，我们计划在独立样品中进一步的基因型和测试遗传结合（n = 1,800）（n = 1,800）（使用嵌套的病例对照组设计：600 FA病例和1,200个匹配的非对照组均来自非抗甲壳的co孔。其中，三分之二是非裔美国人，三分之一是高加索人/西班牙裔。目的2。精细的映射以搜索因果变异：根据目标1a和1b的发现，我们将通过在合并的样本中以重点进行基因分型和关联测试（n = 6000名受试者）（包括1,000 FA Trios和600 FA CASE CASE CASE CASE CASE CASE CASE CASE）（n = 42 00），从而在有希望区域中发现新颖的SNP/CNV（n = 6000名受试者）（n = 6000名受试者）（n = 6000）来自波士顿的控制（n = 1800）。这项拟议的研究将是美国多种族的美国人群中FA的第一个大规模GWA。鉴于有强大的初步数据，独特的资源和团队的记录，它具有很高的成功可能性。这项研究的结果可能会改变我们对FA原因的理解，并为未来的研究提供信息。