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）是由免疫球蛋白（IG）对食品产生的过敏反应引起的，是美国和全球范围内日益增长的临床和公共卫生问题。 FA影响约5-8％的儿童和1-4％的成年人。积极的家族史是过敏性疾病的公认预测指标。我们的初步数据强烈表明遗传因素在FA中起重要作用。迄今为止，很少有FA的遗传研究。该提案的主要重点是进行全基因组关联（GWA）研究，以鉴定FA的易感基因。我们将使用标准方案利用正在进行的多中心FA研究中的生物学样本以及流行病学和临床数据。我们提出了一项两阶段的GWA研究。具体而言，AIM1（第1阶段GWA研究）：我们将使用Illumina Humans1m-Duo Infinium HD Beadchip进行基因型总共500 FA影响的三重奏（母亲，父亲和患有1,500名受试者）。我们将使用最佳可用统计方法测试每个SNP与FA关联。我们将选择达到1阶段显着性（P <10-4）的SNP在第2阶段进行进一步测试。IAM2（第2阶段GWA研究）：我们将基因类型的所有有前途的SNP从AIM 1中鉴定出的所有有前途的SNP，在另一个500 FA受影响的三重奏（母亲，父亲和FA受影响的孩子）中，总计1,500名受试者）。我们将执行联合分析，将结合1,000个三重奏，总共3,000名受试者。我们将在第2阶段使用全基因组的显着性临界值（P <10-7）。鉴于我们对FA的病因有限，缺乏FA的高度有利的候选基因，这项研究将是美国FA的首次大规模GWA研究，GWA研究提供了最佳的可用方法，可以分解FA的遗传基础。这项研究具有以下优势：（1）使用现有的研究样本进行高度成本效益的研究； （2）一个大型样本量可确保足够的统计能力来解决主要目标； （3）利用最先进的高通量基因分型技术和统计方法； （4）一个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对FA的新遗传基因座的鉴定，这将为未来的研究铺平道路。需要进行密集的后续工作，包括独立的复制，精细的映射，测序和功能研究，以进一步阐明哪些特定变体是因果关系，什么是生物学机制，以及它们如何与其他遗传或环境因素相互作用。这项拟议的研究的一个特殊优势在于，鉴于建立良好的基础设施和资源，它为FA的未来研究提供了巨大的潜力。总的来说，这项和未来的研究将有助于建立一个有希望的范式，以识别具有FA高风险的人，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