Analysis of Fatty Liver in the Framingham Heart Study Cohort

描述（由申请方提供）：全球范围内肥胖症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肝衰竭。如果早期发现，肝脏中脂肪的积累可以通过减肥或药物来减少。然而，在大规模人群样本中，脂肪肝的疾病负担、最佳相关性和代谢意义在很大程度上仍然未知。幸运的是，来自心脏研究队列的3500多人，一个超过14,000人的社区和家庭队列，已经有腹部计算机断层扫描（CT），可以量化脂肪肝。在心脏病研究队列中，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可用的3500多个CT扫描，以确定脂肪肝的存在，并确定这种疾病的总体和年龄及性别特异性患病率。目标二。确定脂肪肝的临床相关因素。在一项横断面设计的研究中使用多变量逻辑回归模型，我们将测试肥胖的测量指标（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））以及代谢风险因素（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。确定脂肪肝的遗传度。我们将利用队列中以家族为基础的成分，使用方差成分似然法估计脂肪肝的遗传度。目标4。测试与肥胖和糖尿病相关的遗传变异是否也与脂肪肝相关。我们将测试基因INSIG 2、KCNJ 11、PPARG和7 CF 7 L2中肥胖或糖尿病相关的单核苷酸多态性（SNP）是否也与脂肪肝相关。本申请中提出的工作旨在表征基于大型人群的队列中的脂肪肝，以了解更多关于脂肪肝的临床，生化和遗传相关性以及风险因素的信息。通过更好地了解脂肪肝疾病的危险因素，我们可能能够在疾病过程中更早地识别和治疗脂肪肝患者，从而改善他们的结果。此外，我们将了解脂肪肝的存在是否与临床前心血管疾病的存在相关，而内脏到皮下脂肪沉积可能有助于对这些个体进行风险分层以进行干预。

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.