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

• 批准号: 10414115
• 负责人: Amal Halim Assa'ad
• 金额: $ 23.85万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10414115
• 关键词: Address; Admixture; Affect; African; African American; African American population; African ancestry; 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

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 食物过敏（FA）的伯宁（FA）在少数族裔儿童中占不成比例的高度，尤其是患病率 非裔美国人（AA）的FA的4倍，是欧美（EA）儿童的4倍。花生过敏（PA）是 FA的最常见和严重形式。就像在FA中一样，PA在AA之间表现出相同的种族差异 和EA。尽管关于遗传血统在PA风险中的作用有一个普遍的共识，但程度 祖先的贡献或解释种族分布仍然很大未知。我们的长期目标是确定 遗传血统决定了在AA儿童混合物中有助于总和花生特异性IgE分布。 我们的总体目标是确定花生特异性IgE风险是由遗传血统确定的 AA与非洲血统比例不同的个人混合。我们与收集的良好型PA队列 DNA样品和高密度全基因组多种族全球阵列（MEGA），其中包含SNP集量身定制的SNP集 朝向杂物的祖先提供了一个独特的机会，可以识别特定于祖先的PA风险变体。我们 假设非洲和欧洲血统之间具有较大等位基因频率差异的遗传变异 人口可能是PA风险当前差异的部分原因。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）确定遗传血统和行为 使用多种族基因分型阵列的混合映射；目标2）复制AM中最有希望的变体 使用独立复制队列的峰区。拟议的研究非常重要（考虑到很高 AA儿童中PA的负担）和高度创新（这是第一个混合分析），以解开遗传 与PA相关的祖先特异性风险变体。最重要的是，结果将是少数民族人口 并将为我们的知识以及PA的早期预测，诊断和治疗做出贡献 - 路线图 朝着精确诊断。因此，我们认为这项研究以及未来的研究将发现基本 有关遗传血统是否会影响PA风险和预测的信息，从而减少PA的燃烧 关于患者及其家人并改善生活质量。 1