Identifying genetic and sociodemographic determinants of susceptibility to infectious diseases in diverse population groups

项目摘要 传染病负担的种族/族裔差异很常见，可能加剧现有的社会 不等式除了公正问题之外，健康差距还具有重大的经济后果， 社会上的每个人。以前的研究已经确定了环境因素（例如医疗保健） 访问，社会经济地位，生活方式和结构性种族主义，仅举几例）和人类遗传因素， 对传染病的易感性。然而，对两者进行系统和全面的评估， 缺乏构成传染病族裔/种族差异的社会人口和遗传因素。填充 这一差距对临床护理和公共卫生都很重要。 为此，在这里，我们将利用遗传，电子健康记录和调查数据，从所有美国 生物库，以检验人类遗传因素可能导致传染性疾病中种族/民族差异的假设。 通过以下目标独立于社会人口风险因素的疾病负担： 目标1：确定人口统计学、社会经济学、行为和环境因素， 传染病流行率的种族/民族差异。为此，我们将进行全面的 评估了227个人口统计学、社会经济学、行为和环境变量，通过所有 美国的调查，对336种传染病表型的患病率在精细尺度，遗传定义， 人口社区。在这个目标的最后，我们将知道哪些传染病是丰富的或耗尽的 其中，精细规模的种族/民族社区以及人口统计学、社会经济学、行为学和 环境变量是造成这些差异的主要因素。 目的2：确定导致传染病种族/民族差异的人类遗传因素 普遍性。在这个目标中，我们将深入分析可能与以下疾病相关的遗传变异： 传染病流行。我们将使用互补的方法来评估常见和罕见的遗传 变体。这一目标将导致发现新的传染病易感基因座和风险变体。我们 将进行计算机功能分析，以深入了解这些变体的功能。 在短期内，这项研究将导致确定社会人口和遗传风险因素的基础， 传染病中的种族/民族差异，并了解其对疾病流行的相对贡献。 此外，该项目增强了我们对传染病生物学和遗传因素的理解， 影响对特定病原体易感性的个体间差异。从长远来看，这个项目的结果 可以帮助制定新的公共卫生政策或新的传染病诊断测试或药物。

PROJECT SUMMARY Racial/ethnic disparities in infectious disease burden are common and can exacerbate existing social inequalities. Beyond the question of justice, health disparities have major economic consequences that can affect everyone in society. Previous studies have established the role of both environmental factors (e.g. healthcare access, socioeconomic status, lifestyle, and structural racism, to name a few) and human genetic factors in susceptibility to infectious diseases. However, systematic and comprehensive assessment of both sociodemographic and genetic factors that underlie ethnic/racial disparities in infectious disease is lacking. Filling this gap is important for both clinical care and public health. To this end, here we will leverage the genetic, electronic health records, and survey data from the All of US biobank to test the hypothesis that human genetic factors can contribute to racial/ethnic disparities in infectious disease burden independently of sociodemographic risk factors through the following aims: Aim 1: To identify demographic, socioeconomic, behavioral, and environmental factors that contribute to racial/ethnic disparities in infectious disease prevalence. In this aim, we will perform a comprehensive assessment of 227 demographic, socioeconomic, behavioral, and environmental variables, collected through All of US surveys, on the prevalence of 336 infectious disease phenotypes across fine-scale, genetically-defined population communities. At the end of this aim, we will know which infectious diseases are enriched or depleted in which fine-scale racial/ethnic communities and which demographic, socioeconomic, behavioral, and environmental variables are the main contributors to these disparities. Aim 2: To identify human genetic factors that contribute to racial/ethnic disparities in infectious disease prevalence. In this aim, we will perform in-depth analyses of genetic variants that can be associated with infectious disease prevalence. We will use complementary approaches to assess common and rare genetic variants. This aim will lead to the discovery of novel infectious disease susceptibility loci and risk variants. We will perform in silico functional analysis to gain insight to the function of these variants. In the short term, this study will result in identifying sociodemographic and genetic risk factors that underlie racial/ethnic disparities in infectious diseases and understanding their relative contribution to disease prevalence. Moreover, this project enhances our understanding of infectious disease biology and the genetic factors that affect interindividual variability in susceptibility to specific pathogens. In the long term, the results of this project can help the development of new public health policies or new diagnostic tests or drugs for infectious diseases.