Longitudinal integration of environmental exposures, omics, and childhood NAFLD (LEON) Study

环境暴露、组学和儿童 NAFLD (LEON) 研究的纵向整合

基本信息

批准号：
10744546
负责人：
Tun (Max) M Aung
金额：
$ 80.78万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-12 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10744546
关键词：
Acceleration Adolescent Adult Affect Air Pollution Animal Model Automobile Driving Behavior Behavioral Biological Biological Markers Blood California Chemicals Child Childhood Cirrhosis Clinical Clinical Data Cluster Analysis Communities Complex Cross-Sectional Studies Data Data Science Detection Disease Disease Progression Early identification Endocrine Disruptors Enrollment Environment Environmental Exposure Environmental Pollutants Enzymes Epidemiology Epigenetic Process Ethnic Population Etiology Exposure to Extrahepatic Family Fatty acid glycerol esters Feces Fibrosis Funding Genetic Predisposition to Disease Genomics Goals Health Hepatic High Prevalence Human Industrial Waste Inflammation Investigation Latino Latino Population Life Style Lipids Liver Los Angeles Magnetic Resonance Imaging Measurement Measures Mediation Metabolic Methodology Methods Minority Groups Molecular Molecular Profiling Morbidity - disease rate Multiomic Data Neighborhoods Pathology Pathway interactions Pediatric Hospitals Pesticides Physiological Plasticizers Population Prevalence Prevention approach Prevention strategy Proteomics Public Health Questionnaires Research Research Design Resources Risk Risk Factors Sample Size Severity of illness Social status Specimen Subgroup Toxic Environmental Substances Underserved Population Unhealthy Diet Urine Youth burden of illness chronic liver disease data integration dietary disease phenotype disorder risk epigenomics experience fatty liver disease follow-up health data health disparity hepatocyte injury high dimensionality high risk high risk population imaging modality improved individualized prevention innovation insight lifestyle factors liver injury liver transplantation low socioeconomic status metabolomics metagenomic sequencing microbiome modifiable risk multidisciplinary multiple omics non-alcoholic fatty liver disease nonalcoholic steatohepatitis obesity in children pediatric non-alcoholic fatty liver disease phenotypic data pollutant racial population recruit response social social factors social health determinants specific biomarkers tool toxic metal toxicant transcriptomics trend

项目摘要

ABSTRACT Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the pediatric population with a projected 20% increase in prevalence over the next 10 years. NAFLD in children is more likely than in adults to be characterized by hepatocyte injury in portal regions, reflecting a more severe disease type. Latinos are one of the largest and fastest growing ethnic groups in the US and are disproportionately affected by NAFLD, including a prevalence of cirrhosis that is 9 times the national average. Omics data integration, including genomics, epigenetics, transcriptomics, proteomics, metabolomics, and the microbiome, can provide insight on dysregulation of biological pathways and may help identify risk factors and early molecular indicators of NAFLD risk and disease progression and severity. Studying these specific omics layers in the context of pediatric NAFLD is particularly important to identify both modifiable and non-modifiable risk factors which predispose children to this disease. Environmental pollutant exposures are modifiable exposures that can cause liver injury and contribute to NAFLD risk and disease progression and severity. Numerous widespread chemical pollutants have been associated with fatty liver disease in animal models including persistent industrial pollutants, toxic metals, pesticides, and plasticizers. Previous human studies underscore limitations such as small sample sizes, cross- sectional study design, lack of gold standard imaging methods for NAFLD phenotyping, and lack of focus on Latinos, who are disproportionally affected by NAFLD. Therefore, in response to RFA-HG-22-008, we propose the first and largest longitudinal investigation to integrate multi-omic signatures, environmental exposures, and social and behavioral factors to detect and assess molecular “profiles” characterizing the etiology and progression of NAFLD in Latino youth. Our specific aims are to: (1A) Examine associations between multiple environmental exposures and pediatric NAFLD risk and disease progression and severity in Latino youth; (1B) Evaluate whether these relationships are modified by social factors, behavioral factors, and genetic predisposition; (2A) Identify omics signatures that will serve as biomarkers of NAFLD risk and disease progression and severity; (2B) Evaluate whether these signatures are modified by social and behavioral factors; and (3) Integrate multi-omics data, environmental exposures, social determinants of health and clinical data to identify precise risk profiles of NAFLD risk, and disease progression and severity. Collectively, this study will increase our understanding of NAFLD risk and disease progression in Latino children, who face increasingly higher burdens of the disease. Findings may have broad-reaching clinical and public health implications including precision prevention approaches for pediatric NAFLD in high-risk populations.

抽象的非酒精性脂肪肝病（NAFLD）是小儿种群中最常见的慢性肝病预计未来10年的患病率将增加20％。儿童中的nafld比在儿童中的可能性更大成年人的特征是门户区域的肝细胞损伤，反映了更严重的疾病类型。拉丁美洲人是美国最大，增长最快的族裔之一，受到NAFLD的影响不成比例包括肝硬化的患病率是全国平均水平的9倍。 OMICS数据集成，包括基因组学，表观遗传学，转录组学，蛋白质组学，代谢组学和微生物组可以提供有关有关的见解生物途径失调，可能有助于确定NAFLD的危险因素和早期分子指标风险，疾病的进展和严重程度。在小儿NAFLD的背景下研究这些特定的OMICS层识别可修改和不可修改的危险因素，使儿童容易受到修改和不可修改的危险因素特别重要这种疾病。环境污染物暴露是可修改的暴露，可能导致肝损伤和有助于NAFLD风险，疾病的进展和严重程度。许多宽度化学污染物具有在动物模型中与脂肪肝病有关，包括持续的工业污染物，有毒金属，农药和增塑剂。先前的人类研究强调了限制，例如小样本量，交叉分段研究设计，缺乏用于NAFLD表型的黄金标准成像方法，以及缺乏专注于拉丁美洲人，受NAFLD影响不成比例的。因此，为了回应RFA-HG-22-008，我们提出了整合多摩尼克的签名，环境暴露的第一和最大的纵向投资，以及检测和评估表征病因和表征分子的“概况”的社会和行为因素拉丁裔青年中NAFLD的进展。我们的具体目的是：（1a）检查多个的关联拉丁裔青年的环境暴露和小儿NAFLD风险和疾病的进展和严重程度；（1b）评估这些关系是否通过社会因素，行为因素和遗传来改变倾向；（2a）确定将作为NAFLD风险和疾病的生物标志物的OMICS特征进展和严重程度；（2b）评估这些签名是否是通过社会和行为因素修改的；（3）整合多摩智数据，环境暴露，健康的社会决定者和临床数据确定NAFLD风险以及疾病进展和严重程度的精确风险特征。总的来说，这项研究将提高我们对拉丁裔儿童的NAFLD风险和疾病进展的理解，他们面对越来越多的疾病的伯恩斯较高。调查结果可能具有广泛的临床和公共卫生影响高风险人群中小儿NAFLD的精确预防方法。