Epigenetic Biomarkers of Common Chronic Diseases

描述（由申请人提供）：本申请“常见慢性疾病的表观遗传生物标志物”涉及广泛的挑战领域（03）生物标志物的发现和验证以及特定的挑战主题，03- od -101：使用血细胞中的表观遗传特征来预测疾病。糖尿病、肾病和高血压引起的微血管并发症（脑、外周动脉和冠状动脉）是公众健康的主要负担（1,2），在某些人群亚群中聚集的频率似乎比预期的更频繁。例如，非裔美国人患这些疾病的比例和年龄比非西班牙裔白人更早（3,4）。虽然糖尿病或肾脏疾病的传统诊断标准确定了具有衰弱临床结果高风险的个体，例如截肢和透析，但迫切需要在临床诊断症状出现之前识别高危个体，以避免这些严重的健康结果。影响基因表达的可遗传和不可遗传现象，即表观遗传机制（DNA甲基化、组蛋白修饰和microRNA），在多种细胞过程中发挥关键作用，并被假设为环境因素、生活方式和慢性疾病易感性改变之间的联系（5,6）。DNA甲基化谱的个体间差异有可能在症状前阶段识别出具有疾病发展风险的个体，此时预防措施将是最有益的(7)。DNA甲基化谱，也被称为表观遗传谱，是评估这些慢性疾病表型预测效用的有前途的生物标志物，并且很容易通过外周血样本获得。在过去的14年里，动脉病变遗传流行病学网络一直致力于收集高血压患者微观和宏观血管疾病的临床和亚临床指标及其对肾脏、心脏、大脑和外周动脉的影响。高血压是美国最普遍和高风险的亚群之一。糖尿病在这个高风险亚群中也非常普遍，部分原因是新陈代谢综合症。GENOA研究创造了丰富的生物样本资源（DNA、血清、尿液），以及人口统计学、人体测量学、环境、临床、生化、生理和基因组数据，用于了解慢性疾病及其危险因素的表观遗传预测因子。

DESCRIPTION (provided by applicant): This application, "Epigenetic Biomarkers of Common Chronic Diseases," addresses broad Challenge Area (03) Biomarker Discovery and Validation and specific Challenge Topic, 03-OD-101: Use of Epigenetic Signatures in Blood Cells to Predict Disease. Diabetes, kidney disease, and the microvascular complications from hypertension (in the brain, peripheral arteries, and coronary arteries) are a major burden on the public's health(1, 2) and appear to aggregate in some population subgroups more frequently than expected by chance alone. For example, African-Americans experience these diseases in epidemic proportion and at earlier ages than non-Hispanic Whites(3, 4). While traditional diagnostic criteria for diabetes or kidney disease identify individuals with high risk of debilitating clinical outcomes, such as extremity amputation and dialysis, there is a pressing need to identify at-risk individuals well before the presentation of clinical diagnostic symptoms to avert these severe health outcomes. Heritable and non-heritable phenomena that affect gene expression, known as epigenetic mechanisms (DNA methylation, histone modification, and microRNA), play a key role in multiple cellular processes and have been hypothesized as a link between environmental factors, lifestyle, and alterations in chronic disease susceptibility(5, 6). Inter-individual differences in DNA methylation profiles has the potential to identify individuals at risk for the development of disease outcomes at a presymptomatic stage when preventive efforts will be most beneficial(7). DNA methylation profiles, also known as epigenetic profiles, are promising biomarkers to assess for predictive utility for these chronic disease phenotypes and are easily accessible through peripheral blood samples. For the past 14 years, the Genetic Epidemiology Network of Arteriopathy has been working to collect clinical and subclinical measures of micro and macro vascular disease and its impact on the kidney, heart, brain, and peripheral arteries in hypertensives - one of the most prevalent and high risk subgroups in the US. Diabetes is also highly prevalent in this high risk subgroup due in part to what has been called the metabolic syndrome. The GENOA study has created a rich resource of biological samples (DNA, serum, urine) as well as demographic, anthropometric, environmental, clinical, biochemical, physiological, and genomic data for understanding the epigenetic predictors of chronic diseases and its risk factors. PUBLIC HEALTH RELEVANCE (provided by applicant): This application addresses the specific Challenge Topic, 03-OD-101: Use of Epigenetic Signatures in Blood Cells to Predict Disease and a provides a unique opportunity to examine the utility of epigenetic profiles as biomarkers for predicting chronic disease phenotypes in African-Americans, a group with increased risk of diabetes, kidney disease, and the microvascular complications from hypertension. The goal of this proposed project is to identify new biomarkers of common diseases using epigenetic markers that are measured in the genome of easily accessible blood cells. Our project will investigate these potential epigenetic biomarkers in a high risk subgroup of the population that could benefit greatly from advanced knowledge and increased prevention.