Genetic ancestry differences in IgE- mediated peanut allergy in African Americans

非裔美国人 IgE 介导的花生过敏的遗传祖先差异

基本信息

批准号：
10317528
负责人：
Amal Halim Assa'ad
金额：
$ 19.88万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10317528
关键词：
Address Admixture Affect African African American Age Allergy to peanuts American Asthma Biological Biological Assay Birth Boston Cardiovascular Diseases Case-Control Studies Chicago Child Clinical Clinical Markers Clinical Research Clinical Trials Consensus County DNA Data Data Analyses Diagnosis Disease District of Columbia Environment Environmental Exposure European Exhibits Family Food Hypersensitivity Future Gene Frequency Genetic Genetic Predisposition to Disease Genome Genomic Segment Genotype Goals Health Heritability Hypersensitivity IgE Individual Longitudinal cohort study Malignant neoplasm of prostate Maps Mediating Methods Minority Groups Multiple Sclerosis National Health and Nutrition Examination Survey Obesity Outcome Patient Self-Report Patients Phenotype Population Predisposition Prevalence Public Health Quality of life Recording of previous events Research Design Risk Risk Factors Role Sampling Serum Site Socioeconomic Factors Socioeconomic Status Susceptibility Gene Testing Time Variant admixture mapping ancestry analysis case control caucasian American cohort density food challenge genetic variant genome wide association study genome-wide health care availability improved innovation minority children multi-ethnic novel personalized medicine racial difference racial disparity risk prediction risk variant sex skin prick test

项目摘要

Abstract The burden of food allergy (FA) is disproportionately high among minority children, in particular the prevalence of FA is 4 times higher in African American (AA) than European American (EA) children. Peanut allergy (PA) is the most common and serious form of FA. As in FA in general, PA exhibits the same racial disparity between AA and EA. Although there is a general consensus about the role of genetic ancestry in PA risk, the extent to which ancestry contributes or explains racial disparities remains largely unknown. Our long-term goal is to determine genetic ancestry determinants that contribute to total and peanut specific IgE disparities in admixed AA children. Our overall objective is to determine to what extent peanut specific IgE risk is determined by genetic ancestry in AA admixed individuals with varying African ancestry proportion. Our well-phenotyped PA cohorts with collected DNA samples, and high-density genome-wide Multi-Ethnic Global Array (MEGA) that contains SNP sets tailored towards admixed ancestry presents a unique opportunity to identify ancestry-specific PA risk variants. We hypothesize that genetic variants with large allele frequency differences between African and European ancestry population may be partly responsible for the current difference in PA risk. Two Specific Aims are proposed to test our hypothesis and achieve our proposed plan: Aim 1) Determine the genetic ancestry and conduct admixture mapping using multi-ethnic genotyping array; and Aim 2) Replicate the most promising variants in AM peak regions using independent replication cohorts. The proposed study is highly significant (given the high burden of PA among AA children) and highly innovative (it is the first admixture analysis) to unravel genetic ancestry-specific risk variants associated with PA. Most importantly, the results will be on minority population and will contribute to our knowledge and to the early prediction, diagnosis and treatment of PA—a road map towards precision diagnosis. We therefore believe that this study along with future studies will uncover fundamental information about whether genetic ancestry can affect PA risk and prediction, thereby reducing the burden of PA on patients and their families and improving their quality of life. 1

抽象的少数民族儿童的食物过敏（FA）负担特别高，尤其是患病率非洲裔美国人 (AA) 的 FA 含量是欧洲裔美国人 (EA) 儿童花生过敏 (PA) 的 4 倍。 FA 最常见和最严重的形式与一般 FA 一样，PA 也表现出与 AA 相同的种族差异。尽管对于遗传血统在 PA 风险中的作用存在普遍共识，但其影响程度有多大。血统对种族差异的贡献或解释在很大程度上仍然未知。我们的长期目标是确定。导致混合 AA 儿童中总 IgE 差异和花生特异性 IgE 差异的遗传祖先决定因素。我们的总体目标是确定花生特异性 IgE 风险在多大程度上是由遗传血统决定的。 AA 将具有不同非洲血统比例的个体与我们收集的表型良好的 PA 队列混合在一起。 DNA 样本和包含定制 SNP 集的高密度全基因组多民族全局阵列 (MEGA) 混合血统为识别特定血统的 PA 风险变异提供了独特的机会。培育了非洲和欧洲血统之间等位基因频率差异较大的遗传变异人口可能是目前 PA 风险差异的部分原因。提出了两个具体目标。检验我们的假设并实现我们提出的计划：目标 1) 确定遗传祖先和行为使用多种族基因分型阵列进行混合作图；目标 2) 复制 AM 中最有希望的变异使用独立复制队列的峰值区域拟议的研究非常重要（鉴于高）。 AA 儿童的 PA 负担）和高度创新（这是第一个混合分析）来解开遗传问题最重要的是，结果将针对少数群体。并将有助于我们的知识以及 PA 的早期预测、诊断和治疗——路线图因此，我们相信这项研究以及未来的研究将揭示基本原理。有关遗传血统是否会影响 PA 风险和预测的信息，从而减轻 PA 的负担影响患者及其家人，提高他们的生活质量。 1