Genome-Wide Association Study of Food Allergy

食物过敏的全基因组关联研究

• 批准号: 8116192
• 负责人: XIAOBIN WANG
• 金额: $ 66.45万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-16 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8116192
• 关键词: Address; Adult; Affect; Allergic Disease; Arts; Biological; Candidate Disease Gene; Chicago; Child; Clinical; Clinical Data; Code; Complement; Complex; Copy Number Polymorphism; DNA; Data; Data Collection; Demography; Diagnosis; Environment; Environmental Risk Factor; Epidemiologic Studies; Epidemiology; Etiology; Family history of; Fathers; Food; Food Hypersensitivity; Future; Genes; Genetic; Genetic Heterogeneity; Genetic Markers; Genomics; Genotype; Health Food; Human Genome; Hypersensitivity; ICD-9; IgE; Immunoglobulins; Individual; Interdisciplinary Study; Investigation; Joints; Lead; Maps; Mediating; Mothers; Other Genetics; Physicians; Play; Population; Predisposition; Prevention; Prevention strategy; Protocols documentation; Public Health; Questionnaires; Reaction; Research Design; Research Infrastructure; Resources; Risk; Role; Sample Size; Sampling; Sampling Studies; Skin; Staging; Statistical Methods; Subgroup; Susceptibility Gene; Technology; Testing; Variant; Work; airborne allergen; base; cohort; cost; experience; follow-up; gene environment interaction; genome wide association study; genome-wide; genotyping technology; high risk; molecular scale; novel; prevent; pulmonary function; success; tool; trait

Food allergy (FA), a condition caused by an immunoglobulin (Ig) E-mediated hypersensitivity reaction to food, is a growing clinical and public health problem in the U.S. and worldwide. FA affects approximately 5-8% children and 1-4% of adults. A positive family history is a well-recognized predictor of allergic diseases. Our preliminary data strongly suggest that genetic factors play an important role in FA. To date, few genetic studies of FA have been conducted. The central focus of this proposal is to conduct a genome-wide association (GWA) study to identify susceptibility genes for FA. We will utilize biological samples and epidemiological and clinical data from our ongoing multi-center FA study using a standard protocol. We propose a two-stage GWA study. Specifically, Aim1 (Stage 1 GWA study): We will genotype a total of 500 FA affected trios (mother, father, and FA affected child, a total of 1,500 subjects), using the Illumina Human1M-Duo Infinium HD BeadChip. We will test each SNP for association with FA using best available statistical methods. We will select SNPs reaching Stage 1 significance (p<10-4) to be further tested in Stage 2. Aim2 (Stage 2 GWA study): We will genotype all the promising SNPs identified from Aim 1 in another 500 FA affected trios (mother, father, and FA affected child, a total of 1,500 subjects). We will perform joint analysis that will combine the 1,000 trios, a total of 3,000 subjects. We will use the genome-wide significance cutoff (p<10-7) in Stage 2. This study will be the first large-scale GWA study of FA in the U.S. Given our limited understanding of the etiology of FA and lack of highly favorable candidate genes of FA, a GWA study offers the best available approach to dissect genetic basis of FA. This study has the following strength: (1) a highly cost-efficient study by using existing study samples; (2) a large sample size that assures adequate statistical power for addressing the primary aims; (3) utilization of state-of-the-art, high-throughput genotyping technology and statistical methods; and (4) a highly interactive and experienced multidisciplinary research team. We anticipate that this study will lead to identification of novel genetic loci of FA, which will pave the road for the future investigation. Intensive follow-up work, including independent replications, fine mapping, sequencing, and functional studies, is required to further elucidate which specific variants are causal, what are the biological mechanisms, and how they interact with other genetic or environmental factors. A particular strength of this proposed study is that it offers a tremendous potential for future studies of FA, given the well-established infrastructure and resources. Collectively, this and future studies will help develop a promising paradigm for identifying individuals at high risk of FA, and developing effective strategies for prevention and treatment of FA.

食物过敏 (FA) 是一种由免疫球蛋白 (Ig) E 介导的食物超敏反应引起的疾病，是美国和全世界日益严重的临床和公共卫生问题。 FA 影响大约 5-8% 的儿童和 1-4% 的成人。阳性家族史是公认的过敏性疾病的预测因素。我们的初步数据强烈表明遗传因素在 FA 中发挥着重要作用。迄今为止，对 FA 的遗传学研究很少。该提案的核心重点是进行全基因组关联 (GWA) 研究，以确定 FA 的易感基因。我们将使用标准方案，利用我们正在进行的多中心 FA 研究中的生物样本以及流行病学和临床数据。我们建议进行两阶段 GWA 研究。具体来说，Aim1（第 1 阶段 GWA 研究）：我们将使用 Illumina Human1M-Duo Infinium HD BeadChip 对总共 500 名 FA 受影响的三人组（母亲、父亲和 FA 受影响的孩子，总共 1,500 名受试者）进行基因分型。我们将使用最佳可用的统计方法测试每个 SNP 与 FA 的关联。我们将选择达到第 1 阶段显着性 (p<10-4) 的 SNP，以便在第 2 阶段进行进一步测试。 目标 2（第 2 阶段 GWA 研究）：我们将对另外 500 名 FA 受影响的三人组（母亲、父亲和 FA 受影响的孩子，总共 1,500 名受试者）中从目标 1 中识别出的所有有希望的 SNP 进行基因分型。我们将进行联合分析，将 1,000 个三人组（总共 3,000 个受试者）结合起来。我们将在第二阶段使用全基因组显着性截止值（p<10-7）。这项研究将是美国第一个针对 FA 的大规模 GWA 研究。鉴于我们对 FA 病因的了解有限且缺乏 FA 非常有利的候选基因，GWA 研究提供了剖析 FA 遗传基础的最佳可用方法。本研究具有以下优点：（1）利用现有研究样本进行高成本效益的研究； (2) 样本量大，确保有足够的统计能力来实现主要目标； (3) 利用最先进的高通量基因分型技术和统计方法； (4) 高度互动且经验丰富的多学科研究团队。我们预计这项研究将导致 FA 的新基因位点的鉴定，这将为未来的研究铺平道路。需要深入的后续工作，包括独立复制、精细绘图、测序和功能研究，以进一步阐明哪些特定变异是因果关系、生物学机制是什么以及它们如何与其他遗传或环境因素相互作用。这项拟议研究的一个特殊优势是，鉴于完善的基础设施和资源，它为 FA 的未来研究提供了巨大的潜力。总的来说，这项研究和未来的研究将有助于开发一个有前途的范例，用于识别 FA 高风险个体，并制定预防和治疗 FA 的有效策略。

项目成果

Cardiovascular Risk Factors in Parents of Food-Allergic Children.

食物过敏儿童父母的心血管危险因素。

• DOI: 10.1097/md.0000000000003156
• 发表时间: 2016
• 期刊: Medicine
• 影响因子: 1.6
• 作者: Walker,SheilaOhlsson;Mao,Guangyun;Caruso,Deanna;Hong,Xiumei;Pongracic,JacquelineA;Wang,Xiaobin
• 通讯作者: Wang,Xiaobin