Visceral Adiposity: Genetic and Environmental Influences

内脏肥胖：遗传和环境的影响

• 批准号: 7266840
• 负责人: STEFAN A. CZERWINSKI
• 金额: $ 33.18万
• 依托单位: WRIGHT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-20 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7266840
• 关键词: Abdomen; Accounting; Active Sites; Address; Adipocytes; Adipose tissue; Adverse effects; African American; Age; Alcohol consumption; Analysis of Variance; Architecture; Area; Biological Assay; Budgets; Cardiovascular Diseases; Central obesity; Chromosome Mapping; Complex; Data; Deposition; Depth; Development; Diabetes Mellitus; Diet; Environment; Environmental Risk Factor; Enzyme-Linked Immunosorbent Assay; Etiology; Exposure to; Extended Family; Family; Family Study; Fatty acid glycerol esters; Future; Genes; Genetic; Genetic Models; Genetic Polymorphism; Genome; Genotype; Goals; Heritability; Hormonal; Hormones; Hospitals; Hour; Human; Individual; Inflammation; Inflammatory; Insulin Resistance; Intake; Intra-abdominal; Ionizing radiation; Knowledge; Light; Localized; Logistics; Macronutrients Nutrition; Magnetic Resonance Imaging; Maps; Measures; Mediating; Metabolic; Metabolic syndrome; Methods; Modeling; Modems; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Obesity; Ohio; Organ; Participant; Phenotype; Physical activity; Physiological; Plasma; Play; Population Study; Procedures; Production; Protocols documentation; Quantitative Genetics; Quantitative Trait Loci; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Research Project Grants; Research Support; Residual state; Resources; Risk; Risk Factors; Role; Signal Transduction; Site; Slice; Smoking; Structure; Thinking; Time; Tobacco; Variant; Visceral; X-Ray Computed Tomography; aging gene; base; cardiovascular disorder risk; cost; day; diabetes risk; disorder risk; gene environment interaction; genetic analysis; genetic linkage analysis; genetic pedigree; kindred; member; novel; programs; sex; subcutaneous; time use; trait; vascular inflammation

DESCRIPTION (provided by applicant): The goal of the proposed study is to understand the genetic architecture underlying visceral obesity and its associated physiological components. Accumulation of fat deep within the abdomen (i.e., visceral adipose tissue) is known to play a pivotal role in the development of non-insulin dependent diabetes mellitus and cardiovascular disease (CVD). In our proposed study, we aim to disentangle the genetic and environmental factors that explain human variation in visceral adiposity by viewing it as a component of a phenotypic complex that also includes insulin resistance, vascular inflammation, and hormonal variations (the "visceral obesity complex"). The proposed study is built upon an existing study of 1,000 individuals in five large multi-generational kindreds, in which whole-genome genotyping and disease risk factor phenotyping are already underway. The proposed study has three specific aims. In Specific Aim 1 we will phenotype the study population using MRI and dual energy x-ray absorptiometry to measure the amount and distribution of visceral and subcutaneous adipose tissue, using ELISA to assay concentration of adipocyte-derived hormones, and using a repeated 24-hour dietary recall protocol to characterize current energy and macronutrient intake. In Specific Aim 2 we will use variance components-based quantitative genetic methods for extended pedigrees to estimate the heritability of the independent components of the visceral obesity complex, identify key environmental variables and covariates (i.e., sex, age, diet, physical activity, hormone usage, smoking and alcohol consumption) that influence the visceral obesity complex alone or in interaction with genetic factors, and examine the extent to which common genetic factors underlie this complex of closely related traits. In Specific Aim 3, we will use variance components-based linkage methods to identify quantitative trait loci (QTL) harboring genes that influence variation in constituent components of the visceral obesity complex. We also will examine gene-by-environment, gene-by-sex, and gene-by-age interactions in these traits. Fine mapping procedures will be used further localize QTL that are identified. At the conclusion of the proposed study, we will have identified particular genetic loci that influence the visceral obesity complex, and will better understand how particular genotypes may, when confronted with particular environments, predispose individuals to the accumulation of visceral adipose tissue, thereby putting them at increased future risk for developing diabetes and CVD.

描述（由申请人提供）：拟议的研究的目的是了解内脏肥胖的基础遗传结构及其相关的生理成分。众所周知，腹部深处脂肪的积累在非胰岛素依赖性糖尿病和心血管疾病（CVD）中起着关键作用。在我们提出的研究中，我们旨在通过将其视为表型复合物的组成部分来解释分解内脏肥胖的遗传和环境因素，该表型复合物也包括胰岛素抵抗，血管炎症和荷尔蒙变异（“粘性肥胖络合物”）。拟议的研究建立在对五个大型多代亲属中的1,000名个人的现有研究基础上，其中全基因组基因分型和疾病危险因素的表型已经在进行中。 拟议的研究具有三个具体目标。在特定目标1中，我们将使用MRI和双能X射线吸收仪表型表型，以测量内脏和皮下脂肪组织的数量和分布，使用ELISA来测定脂肪细胞衍生的激素的浓度，并使用反复的24小时饮食召回方案来表征当前的能量和毛孔摄入量。在特定目标2中，我们将使用基于方差的定量遗传学方法进行扩展的分子，以估计内脏肥胖症复合物的独立组成部分的遗传力，识别关键的环境变量和协变量（即，性，年龄，年龄，饮食，饮食，身体活动，吸烟和饮酒的疾病，均具有肥胖的范围，均与肥胖相比，遗传因素是这种密切相关特征的复合体。在特定的目标3中，我们将使用基于方差的链接方法来识别携带基因的定量性状基因座（QTL），这些基因会影响内脏肥胖络合物的成分成分变化。我们还将检查这些特征中的基因，环境基因，基因和基因相互作用。精细的映射过程将用于进一步的定位QTL。 在拟议的研究结束时，我们将确定影响内脏肥胖症复合物的特定遗传基因座，并更好地理解特定的基因型在面对特定环境时可能会如何使个体的积累，从而使他们的糖尿病和糖尿病和CVD的未来风险增加。