Mechanisms of Advanced NAFLD Disparities in Hispanics: A Multi-level Analysis

西班牙裔晚期 NAFLD 差异的机制：多层次分析

• 批准号: 10530687
• 负责人: VERONICA WENDY SETIAWAN
• 金额: $ 61.5万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10530687
• 关键词: Affect; Automobile Driving; Bioinformatics; Biological; Cells; Cholesterol; Cirrhosis; Clinical; Clinical Data; Complex; County; Data; Development; Diagnostic; Dietary Factors; Disease; Disease Progression; Disparity; Enrollment; Environment; Environmental Risk Factor; Ethnic Origin; Ethnic Population; Etiology; Evaluation; Fibrosis; Genes; Genetic; Genetic Predisposition to Disease; Genetic Variation; Goals; Hepatic; Heterogeneity; High Prevalence; Hispanic; Hispanic Populations; Hospitals; Immigrant; Immune; Immune Targeting; Immune response; Immunologic Factors; Incidence; Inflammation; Intake; Life Style; Lipids; Liver; Liver Fibrosis; Los Angeles; Metabolic; Methods; Mitochondria; Modernization; Morbidity - disease rate; Natural History; Neighborhoods; Not Hispanic or Latino; Nuclear; Pathology; Patients; Performance; Peripheral; Phenotype; Plasma Proteins; Population; Population Heterogeneity; Prevalence; Primary carcinoma of the liver cells; Questionnaires; RNA; Race; Recording of previous events; Research; Risk Factors; Severities; Severity of illness; Societies; Specimen; Subgroup; Tissue-Specific Gene Expression; Ultrasonography; chronic liver disease; contextual factors; dietary; disease disparity; disorder risk; ethnic disparity; ethnic diversity; gene discovery; genetic variant; health disparity; high risk; high risk population; improved; innovation; insight; lifestyle factors; liver inflammation; liver transplantation; migration; mortality; multidisciplinary; multilevel analysis; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel; outcome prediction; polygenic risk score; prospective; protein biomarkers; protein expression; racial population; recruit; response; single-cell RNA sequencing; social; social factors; social influence; sociodemographic factors; therapeutic target; trait; transcriptomic profiling; transcriptomics

PROJECT SUMMARY/ABSTRACT Nonalcoholic fatty liver disease (NAFLD) leading to nonalcoholic steatohepatitis (NASH) is a major cause of chronic liver disease that may progress to cirrhosis and hepatocellular carcinoma (HCC). Considering the prevalence, particularly among Hispanics, understanding the etiology and mechanisms of this disease by race/ethnicity is imperative. We have established a multidisciplinary team to comprehensively characterize the dynamic interplay of multiple factors (genetics, lifestyle, environmental and immune factors) in NAFLD/NASH and the underlying mechanisms driving incidence, severity and progression that result in health disparities in Hispanics. We will identify factors associated with NAFLD development and progression in Hispanics and non- Hispanic whites (NHW) in Los Angeles County (LAC). The large immigrant populations in LAC offer unique perspectives and opportunities to examine health disparities in Hispanics. We will enroll 2,000 patients (1,000 Hispanics and 1,000 NHW) with FibroScan-confirmed advanced (>F2) and mild (≤F1) hepatic fibrosis and 1,000 matched controls without ultrasonographic evidence of NAFLD recruited from the LAC and USC Keck Hospitals. We will collect biological specimens, clinical and detailed questionnaire data for sociodemographic and risk factors and use geospatial approaches to ascertain social and neighborhood-related factors. Case groups will be followed prospectively for disease progression. Our specific aims are 1) to determine the contribution of lifestyle, clinical, social/environmental factors and genetics (nuclear and mitochondrial) to ethnic disparities in NAFLD risk, disease severity (advanced/mild fibrosis) in Hispanics and NHW; 2) to examine how differential gene expression revealed by scRNA-transcriptomic profiling of circulating innate immune cells in NAFLD varies according to polygenic risk scores and dietary factors; utilize bioinformatics approach to identify plasma proteins with diagnostic and predictive accuracy for NAFLD severity and progression; 3) to identify high-risk groups for NAFLD risk and progression by integrating genetics, lifestyle, clinical, social and contextual factors in Hispanics and NHW using an innovative latent variable analysis. Our study will culminate in novel, comprehensive, and innovative characterization of multi-level factors associated with phenotypic spectrum of NAFLD and disease progression and contribute significantly to the understanding of the etiology and mechanisms that influence disparities in NAFLD in high-risk Hispanic population.

项目摘要/摘要 非酒精性脂肪肝病（NAFLD）导致非酒精性脂肪性肝炎（NASH）是导致的主要原因 可能发展为肝硬化和肝细胞癌（HCC）的慢性肝病。考虑到 患病率，特别是在西班牙裔中，了解这种疾病的病因和机制 种族/种族是必须的。我们已经建立了一个多学科团队，以全面地描述 NAFLD/NASH中多种因素（遗传学，生活方式，环境和免疫因素）的动态相互作用 以及驾驶事件的基本机制，导致健康分布的严重性和进步 西班牙裔。我们将确定与NAFLD发展和西班牙裔和非 - 非国家发展相关的因素 洛杉矶县（LAC）的西班牙白人（NHW）。 LAC中的大移民人口提供独特 观察西班牙裔健康差异的观点和机会。我们将注册2,000名患者（1,000名 西班牙裔和1,000 nhw），纤维化固定的高级（> f2）和轻度（≤f1）肝纤维化和1,000 匹配的控制措施，没有从LAC和USC Keck医院招募的NAFLD的超声检查证据。 我们将收集社会人口统计学和风险的生物标本，临床和详细的问卷数据 因素并使用地理空间方法来确定社会和邻里相关的因素。案例组将 前瞻性地遵循疾病进展。我们的具体目的是1）确定 生活方式，临床，社会/环境因素和遗传学（核和线粒体）到种族差异 NAFLD风险，西班牙裔和NHW中的疾病严重程度（晚期/轻度纤维化）； 2）检查如何差异 基因表达通过nafld中循环先天免疫球的SCRNA-转录分析揭示 根据多基因风险评分和饮食因素；利用生物信息学方法识别血浆蛋白 具有NAFLD严重性和进展的诊断和预测精度； 3）确定高风险群体的 NAFLD风险和进步通过整合遗传学，生活方式，临床，社会和情境因素 和NHW使用创新的潜在变量分析。我们的研究将在新颖，全面和 与NAFLD和疾病的表型相关的多层次因子的创新表征 进步并有助于理解影响的病因和机制 NAFLD高危西班牙裔人口的差异。