Analysis of Fatty Liver in the Framingham Heart Study Cohort

描述（由申请人提供）：世界范围内肥胖的增加伴随着糖尿病、高血压、血脂异常和非酒精性脂肪性肝病（NAFLD）的增加。NAFLD可导致肝硬化和最终的肝功能衰竭。如果及早发现，可以通过减肥或药物治疗来减少肝脏中脂肪的堆积。然而，在基于大量人群的样本中，脂肪肝的疾病负担、最佳相关因素和代谢意义在很大程度上仍然未知。幸运的是，来自Framingham心脏研究队列（一个社区和家庭为基础的队列，超过14,000人）的3500多人进行了腹部计算机断层扫描（ct），可以量化脂肪肝。在弗雷明汉心脏研究队列中，我们提出：目标1。确定脂肪肝的患病率。我们将阅读本研究样本中3500多份可用的CT扫描，以了解脂肪肝的存在，并确定这种疾病的总体患病率、年龄和性别特异性患病率。目标2。确定脂肪肝的临床相关因素。在一项横断面设计的研究中，我们将使用多变量logistic回归模型，检验肥胖指标（包括体重指数（BMI）、腰围（WC）、皮下脂肪组织（SAT）和内脏脂肪组织（VAT））以及代谢危险因素（包括空腹血糖受损（IFG）、糖尿病（DM）、高血压（HTN）和血脂异常）是否与脂肪肝独立相关。此外，我们将测试冠状动脉钙的存在是否与脂肪肝相关。目标3。确定脂肪肝的遗传性。我们将利用队列中基于家庭的成分，使用方差成分似然方法来估计脂肪肝的遗传性。目标4。检测与肥胖和糖尿病相关的基因变异是否也与脂肪肝有关。我们将测试肥胖或糖尿病相关基因INSIG2、KCNJ11、PPARG和7CF7L2的单核苷酸多态性（snp）是否也与脂肪肝有关。本应用程序提出的工作旨在以大人群为基础的队列研究脂肪肝的特征，以更多地了解脂肪肝的临床、生化和遗传相关因素及其危险因素。随着对脂肪肝风险因素的更好了解，我们可能能够在脂肪肝患者的疾病过程中更早地识别和治疗他们，从而改善他们的预后。此外，我们将了解与内脏到皮下脂肪沉积相比，脂肪肝的存在是否与临床前心血管疾病的存在相关，这可能有助于对这些个体进行干预的风险分层。

DESCRIPTION (provided by applicant): The worldwide increase in obesity has been accompanied by an increase in diabetes, hypertension, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD). NAFLD can result in liver cirrhosis and eventual liver failure. If detected early, accumulation of fat in the liver can be reduced with weight loss or medications. The burden of disease from, best correlates of, and metabolic significance of fatty liver in large population-based samples however, remain largely unknown. Fortunately, over 3500 individuals from the Framingham Heart Study cohort, a community and family-based cohort of over 14,000 individuals, have had abdominal computed tomograms (CTs) which can be quantified for fatty liver. In the Framingham Heart Study Cohort we propose to: Aim 1. Determine the prevalence of fatty liver. We will read the over 3500 CT scans available in this study sample for the presence of fatty liver and determine the overall and age and sex-specific prevalence of this condition. Aim 2. Determine the clinical correlates of fatty liver. Using multivariate logistic regression modeling in a cross sectionally designed study, we will test whether measures of adiposity including body mass index (BMI), waist circumference (WC), subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) as well as metabolic risk factors including impaired fasting glucose (IFG), diabetes (DM), hypertension (HTN) and dyslipidemia independently correlate with fatty liver. Furthermore, we will test whether the presence of coronary artery calcium correlates with fatty liver. Aim 3. Determine the heritability of fatty liver. We will take advantage of the family-based component of the cohort to estimate the heritability of fatty liver using variance-components likelihood methods. Aim 4. Test whether genetic variants that are associated with obesity and diabetes are also associated with fatty liver. We will test whether obesity or diabetes-associated single nucleotide polymorphisms (SNPs) in genes INSIG2, KCNJ11, PPARG, and 7CF7L2 also associate with fatty liver. The work proposed in this application aims to characterize fatty liver in a large population based cohort to learn more about the clinical, biochemical and genetic correlates and risk factors of fatty liver. With a better understanding of fatty liver disease risk factors we may be able to identify and treat people with fatty liver earlier in the course of their disease and thus improve their outcome. Furthermore, we will learn whether the presence of fatty liver correlates with the presence of preclinical cardiovascular disease compared to visceral to subcutaneous deposition of fat which may help risk stratify such individuals for intervention.