Genetic Architecture of Obesity and Inflammation in Hispanic Americans

西班牙裔美国人肥胖和炎症的遗传结构

基本信息

批准号：
8547075
负责人：
Nicholette D. Allred
金额：
$ 17.85万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-20 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8547075
关键词：
Adipose tissue Admixture Architecture Atherosclerosis Biological Markers Body mass index C-reactive protein Candidate Disease Gene Cardiovascular Diseases Computer Simulation Data Data Analyses Development Diabetes Mellitus Disease Epidemic Family Family Study Fatty acid glycerol esters Fibrinogen Funding Genetic Genetic Determinism Genetic Models Genetic Variation Genomics Goals Haplotypes Health Heart Diseases Heritability Hispanic Americans Hispanics Human Incidence Inflammation Inflammatory Insulin Resistance Interleukin-6 Liver Liver diseases Maps Measures Meta-Analysis Metabolic Minority Minority Groups National Heart, Lung, and Blood Institute National Institute of Diabetes and Digestive and Kidney Diseases Obesity Outcome Pathogenesis Phenotype Plasminogen Activator Inhibitor 1 Population Prevalence Proteins Public Health Recruitment Activity Research Research Design Retinol Binding Proteins Sampling Severities TNF gene Testing Tumor Necrosis Factor Receptor Variant Visceral X-Ray Computed Tomography adiponectin base blood glucose regulation cohort density design exome exome sequencing genetic analysis genetic linkage analysis genetic pedigree genetic variant genome wide association study high risk insight non-alcoholic fatty liver novel novel therapeutics simulation statistics subcutaneous tool trait waist circumference

项目摘要

DESCRIPTION (provided by applicant): Obesity is rapidly becoming an epidemic in the US with an increasing prevalence and severity of consequence among minority populations. Obesity induces an inflammatory state that is implicated in adverse health conditions, e.g. insulin resistance, diabetes and non-alcoholic fatty liver disease. The over-arching goal of this proposal is to identify common and rare genetic variants underlying variation in quantitative intermediate phenotypes of obesity and inflammation in the largest US minority group, Hispanics. In the Insulin Resistance Atherosclerosis Family Study (IRASFS; funded for two five-year cycles by NHLBI and now funded under the GUARDIAN Consortium by NIDDK to study glucose homeostasis genetics) we have recruited a large Hispanic cohort and obtained detailed and novel measures of obesity, glucose homeostasis and relevant biomarkers. Through heritability, linkage, candidate gene and pilot genome-wide association studies (GWAS), we have explored the genetic determinants and identified potential loci associated with a subset of these traits. In this application, we propose to extend these findings through secondary analysis of existing GWAS, exome sequencing and candidate gene data in an effort to identify common and rare genetic variation associated with obesity and inflammation. The strengths of the proposed study include the large pedigrees in our Hispanic cohort, highly detailed, quantitative obesity and inflammation phenotypes not previously examined via GWAS, measured biomarkers that are more proximal to the gene products than aggregate traits, e.g. diabetes and heart disease, development of a novel analytic tool designed to increase the power to detect uncommon SNP associations with quantitative traits and our long-standing, highly productive collaborative team. The proposed research has the potential to impact our understanding of the genetic architecture of obesity and inflammation, traits intertwined with diabetes and heart disease, in the fastest growing US minority population.

描述（由申请人提供）：肥胖正在美国迅速成为一种流行病，少数族裔人群的患病率和后果的严重性不断增加。肥胖会引起炎症状态，从而导致不利的健康状况，例如肥胖。胰岛素抵抗、糖尿病和非酒精性脂肪肝。该提案的首要目标是确定美国最大的少数族裔西班牙裔肥胖和炎症的定量中间表型变异背后的常见和罕见遗传变异。在胰岛素抵抗动脉粥样硬化家族研究（IRASFS；由 NHLBI 资助两个五年周期，现在由 NIDDK 在 GUARDIAN 联盟资助，研究葡萄糖稳态遗传学）中，我们招募了一个大型西班牙裔队列，并获得了详细且新颖的肥胖测量方法，葡萄糖稳态和相关生物标志物。通过遗传性、连锁、候选基因和试点全基因组关联研究 (GWAS)，我们探索了遗传决定因素并确定了与这些性状子集相关的潜在位点。在此应用中，我们建议通过对现有 GWAS、外显子组测序和候选基因数据的二次分析来扩展这些发现，以努力识别与肥胖和炎症相关的常见和罕见的遗传变异。拟议研究的优点包括我们的西班牙裔队列中的大谱系、高度详细、定量的肥胖和炎症表型（以前未通过 GWAS 检查）、测量的生物标志物比总体性状更接近基因产物，例如糖尿病和心脏病，开发一种新型分析工具，旨在提高检测不常见的 SNP 与数量性状关联的能力，以及我们长期、高效的协作团队。这项拟议的研究有可能影响我们对美国增长最快的少数族裔人口中肥胖和炎症的遗传结构以及与糖尿病和心脏病交织在一起的特征的理解。