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

摘要 食物过敏（FA）的负担在少数民族儿童中不成比例地高，特别是患病率 非裔美国人（AA）的FA是欧裔美国人（EA）儿童的4倍。花生过敏（PA） 最常见和最严重的FA形式。与一般FA一样，PA在AA和AA之间表现出相同的种族差异， 和EA。虽然关于遗传祖先在PA风险中的作用存在普遍共识，但在多大程度上， 血统造成或解释种族差异的情况在很大程度上仍然不为人所知。我们的长期目标是确定 遗传祖先的决定因素，有助于总的和花生特异性IgE的混合AA儿童的差异。 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祖先决定的， AA混合不同非洲血统比例的个体。我们收集了具有良好表型的PA队列， DNA样本和高密度全基因组多种族全球阵列（MEGA），其中包含定制的SNP集 混合血统的研究提供了一个独特的机会，以确定祖先特异性PA风险变异。我们 假设在非洲和欧洲血统之间具有较大等位基因频率差异遗传变异 人群可能是目前PA风险差异的部分原因。提出了两个具体目标， 测试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的混合物作图;和目的2）在AM中复制最有希望的变体 使用独立复制队列的峰值区域。这项研究非常重要（考虑到高 AA儿童中PA的负担）和高度创新（这是第一个混合物分析），以解开遗传 与PA相关的祖先特异性风险变异。最重要的是，结果将在少数民族人口 并将有助于我们的知识和PA的早期预测，诊断和治疗-路线图 精确诊断的方法因此，我们相信这项研究沿着未来的研究将揭示基本的 关于遗传祖先是否会影响PA风险和预测的信息，从而减轻PA的负担 对患者及其家属的影响，并改善他们的生活质量。 1

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