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

确定不同人群中传染病易感性的遗传和社会人口学决定因素

• 批准号: 10795339
• 负责人: Samira Asgari
• 金额: $ 25.35万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-17 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10795339
• 关键词: Accounting; Affect; Behavioral; Biology; COVID-19 disparity; Categories; Code; Communicable Diseases; Communities; Complex; Data; Data Set; Development; Diagnostic tests; Disease; Disparity; Economics; Electronic Health Record; Environmental Risk Factor; Equity; Ethnic Origin; Ethnic Population; Future; Gene Expression; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genome; Genomic Segment; Genotype; Geography; Goals; HIV; HIV/AIDS; Health Policy; Hepatitis; Human; Human Genetics; Inequality; Justice; Life Style; Malaria; Names; Participant; Patient Self-Report; Pharmaceutical Preparations; Population; Population Group; Population Heterogeneity; Positioning Attribute; Predisposition; Prevalence; Public Health; Race; Rare Diseases; Recording of previous events; Research Personnel; Residual state; Resources; Respiratory Tract Infections; Risk Factors; Role; Sepsis; Sexually Transmitted Diseases; Shapes; Societies; Socioeconomic Status; Stratification; Structural Racism; Structure; Surveys; Susceptibility Gene; Testing; Tuberculosis; Variant; Work; admixture mapping; biobank; burden of illness; clinical care; cohort; disease phenotype; epidemiology study; ethnic difference; ethnic disparity; ethnic minority; experience; genetic analysis; genetic risk factor; genetic variant; genome sequencing; genome wide association study; health care availability; health disparity; human genomics; improved; in silico; insight; inter-individual variation; low socioeconomic status; novel; novel diagnostics; novel marker; novel therapeutics; pathogen; racial difference; racial disparity; racial minority; rare variant; risk variant; social disparities; sociodemographic factors; sociodemographic variables; sociodemographics; socioeconomics; whole genome

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.

项目概要 传染病负担方面的种族/族裔差异很常见，并且可能加剧现有的社会负担 不平等。除了正义问题之外，健康差异还具有重大的经济后果，可能影响 社会上的每个人。先前的研究已经确定了这两种环境因素（例如医疗保健）的作用 机会、社会经济地位、生活方式和结构性种族主义等）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 缺乏构成传染病种族差异的社会人口和遗传因素。填充 这一差距对于临床护理和公共卫生都很重要。 为此，我们将利用来自全美的遗传、电子健康记录和调查数据 生物库测试人类遗传因素可能导致传染性种族/民族差异的假设 通过以下目标，疾病负担独立于社会人口学危险因素： 目标 1：确定人口、社会经济、行为和环境因素 传染病患病率的种族/民族差异。为了这个目标，我们将进行全面的 对通过 All 收集的 227 个人口、社会经济、行为和环境变量进行评估 美国对 336 种传染病表型的流行情况进行的调查，涵盖精细范围、基因定义 人口社区。在这个目标结束时，我们将知道哪些传染病被丰富或耗尽 其中有精细规模的种族/民族社区，以及人口、社会经济、行为和 环境变量是造成这些差异的主要因素。 目标 2：确定导致传染病种族/民族差异的人类遗传因素 流行率。为此，我们将对可能与以下疾病相关的遗传变异进行深入分析： 传染病流行率。我们将使用补充方法来评估常见和罕见的遗传 变体。这一目标将导致新的传染病易感位点和风险变异的发现。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，这项研究将确定潜在的社会人口和遗传风险因素 传染病的种族/民族差异并了解其对疾病流行的相对影响。 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 影响个体对特定病原体易感性的差异。从长远来看，该项目的成果 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。