Epigenetic Age Acceleration and Psychoneurological Symptoms in Sickle Cell Disease

镰状细胞病的表观遗传年龄加速和精神神经症状

基本信息

批准号：
10594523
负责人：
ALLISON E ASHLEY-KOCH
金额：
$ 20.13万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-18 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10594523
关键词：
Acceleration Adult Affect Age Aging Assessment tool Biological Biological Factors Biological Markers Black Populations Blood Blood specimen Cell Aging Cessation of life Characteristics Chronic Chronic Disease Chronology Cross-Sectional Studies DNA DNA Methylation Data Data Reporting Data Set Development Discrimination Epigenetic Process Generations Goals Health Health Promotion Health Status Impaired cognition Individual Inflammation Intervention Longevity Maintenance Measures Methods Methylation Molecular Mood Disorders Outcome Oxidative Stress Pain Patient Outcomes Assessments Patient Self-Report Patients Persons Physiological Processes Population Process Quality of life Reduce health disparities Registries Reporting Research Risk Assessment Sampling Sickle Cell Anemia Sleep disturbances Strategic Planning Stress Symptoms Tissues Underrepresented Populations United States Universities Variant cognitive function depressive symptoms design experience health disparity high risk immunosenescence insight inter-individual variation interest methylation pattern mitochondrial dysfunction mortality novel premature psychosocial racism social determinants

项目摘要

PROJECT SUMMARY Individuals with sickle cell disease (SCD) experience deleterious psychoneurological symptoms, such as pain, sleep disturbances, depressive symptoms, and cognitive impairment. Among these symptoms, there is notable interindividual variability. Few studies have sought to examine why some individuals experience worse psychoneurological symptoms than others. Identifying biological factors, such as epigenetic mechanisms that influence the variability of symptom experiences in SCD, can help inform the development of risk assessment tools and interventions that promote health maintenance, quality of life, and reduce health disparities in this population. Recent evidence has converged to suggest a person's epigenetic age may be associated with psychoneurological symptom experiences in SCD. Epigenetic age is calculated by assessing DNA methylation patterns at numerous CpG loci that account for the pace of cellular aging or declining tissue function. Premature epigenetic age acceleration putatively involves many physiologic processes, including increased inflammation, oxidative stress, and mitochondrial dysfunction. Associations with epigenetic age acceleration and psychoneurological symptom experiences in other chronic disease populations has recently been identified. However, whether epigenetic age acceleration occurs and if it is associated with these symptoms in individuals with SCD remains unknown. The specific aims of this cross-sectional study are to 1) characterize epigenetic aging DNA methylation patterns and determine presence of epigenetic age acceleration and 2) identify associations between epigenetic age acceleration and psychoneurological symptoms (pain, sleep disturbances, depressive symptoms, and cognitive function) in adults with SCD. DNA samples and patient- reported outcome data already collected at Duke University as part of the Sickle Cell Disease Consortium Research Registry (n=92) will be used in this study. DNA methylation data will be generated from the extracted DNA of blood specimens and used to calculate epigenetic age. Because different epigenetic clocks provide different measures and characteristics of epigenetic aging, epigenetic age acceleration will be calculated using three epigenetic clocks (Horvath, Hannum, and Levine). We will also examine whether the calculations from each of the clocks are correlated in the sample. Patient-reported data for each symptom of interest existing in the SCDIC Registry will be used to determine associations with epigenetic age acceleration for each of the epigenetic clocks. This “high risk, high return” study may provide novel insight into epigenetic aging biomarkers associated with symptom development and health outcomes in people with SCD, an underrepresented population. The data generated is essential for designing a rigorous and adequately powered R01 study to understand the interactions of multiple level factors (e.g., epigenetic age acceleration, social determinants such as discrimination and racism) that contribute to symptom burden and health disparities in this population.

项目概要镰状细胞病 (SCD) 患者会经历有害的精神神经症状，例如疼痛、在这些症状中，睡眠障碍、抑郁症状和认知障碍是值得注意的。很少有研究试图探究为什么有些人的经历更糟。识别生物因素，例如表观遗传机制。影响 SCD 症状经历的变异性，有助于为风险评估的制定提供信息促进健康维护、生活质量并减少健康差距的工具和干预措施最近的证据表明一个人的表观遗传年龄可能与人口有关。 SCD 的精神神经症状经历是通过评估 DNA 甲基化来计算的。许多 CpG 位点的模式可解释细胞衰老或组织功能下降的速度。过早的表观遗传年龄加速可能涉及许多生理过程，包括增加炎症、氧化应激和线粒体功能障碍与表观遗传年龄加速的关联。最近，其他慢性病人群的心理神经症状经历然而，表观遗传年龄加速是否发生以及是否与这些症状相关。患有 SCD 的个体仍然未知。这项横断面研究的具体目的是 1) 描述特征。表观遗传衰老 DNA 甲基化模式并确定表观遗传年龄加速的存在和 2) 确定表观遗传年龄加速与精神神经症状（疼痛、睡眠患有 SCD 的成人 DNA 样本和患者的紊乱、抑郁症状和认知功能。报告的结果数据已在杜克大学作为镰状细胞病联盟的一部分收集本研究将使用研究登记处 (n=92) 从提取的 DNA 甲基化数据中生成。血液样本的 DNA 并用于计算表观遗传年龄，因为不同的表观遗传时钟提供。表观遗传衰老的不同衡量标准和特征，表观遗传年龄加速将使用以下方法计算我们还将检查三个表观遗传时钟（Horvath、Hannum 和 Levine）是否来自计算。每个时钟在样本中与患者报告的每个感兴趣症状的数据相关。 SCDIC 登记系统将用于确定每个基因与表观遗传年龄加速的关联这项“高风险、高回报”的研究可能为表观遗传衰老生物标志物提供新的见解。与 SCD 患者的症状发展和健康结果相关，但代表性不足生成的数据对于设计严格且充分有力的 R01 研究至关重要。了解多层次因素的相互作用（例如表观遗传年龄加速、社会决定因素等）歧视和种族主义），这些因素导致了该人群的症状负担和健康差异。