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

• 批准号: 10449461
• 负责人: ALLISON E ASHLEY-KOCH
• 金额: $ 24.15万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 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/10449461
• 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

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.

项目摘要 患有镰状细胞疾病（SCD）的人经历了删除的心理学症状，例如疼痛， 睡眠障碍，抑郁症状和认知障碍。在这些症状中，有明显的 个体间的变异性。很少有研究感觉到为什么有些人会经历更糟的原因 心理功能症状比其他人。识别生物学因素，例如表观遗传机制 影响SCD症状经历的可变性，可以帮助您告知风险评估的发展 促进健康维护，生活质量并减少健康差异的工具和干预措施 人口。最近有证据表明一个人的表观遗传年龄可能与 SCD中的心理外科症状经历。通过评估DNA甲基化来计算表观遗传年龄 众多CPG基因座的模式，这些模式解释了细胞衰老或组织功能下降的空间。 过早的表观遗传年龄加速涉及许多生理过程，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 最近在其他慢性疾病人群中的心理学症状经历 确定。但是，是否发生表观遗传年龄加速以及与这些症状有关 患有SCD的人仍然未知。这项横断面研究的具体目的是1）表征 表观遗传性衰老DNA甲基化模式并确定表观遗传年龄加速的存在，2） 确定表观遗传年龄加速与心理学症状之间的关联（疼痛，睡眠 SCD成人的障碍，抑郁症状和认知功能）。 DNA样品和患者 - 报道了杜克大学已经收集的结果数据作为镰状细胞疾病财团的一部分 研究注册表（n = 92）将在本研究中使用。 DNA甲基化数据将从提取的 血液标本的DNA，用于计算表观遗传年龄。因为不同的表观遗传钟提供 表观遗传衰老，表观遗传年龄加速的不同措施和特征将使用 三个表观遗传钟（Horvath，Hannum和Levine）。我们还将检查是否计算 样本中的每个时钟都相关。患者报告的每种感兴趣症状的数据 SCDIC注册中心将用于确定每个与表观遗传年龄加速的关联 表观遗传钟。这项“高风险，高回报”研究可能会提供对表观遗传衰老生物标志物的新见解 与SCD患者的症状发展和健康成果相关，这是人为不足的 人口。生成的数据对于设计严格且功能齐全的R01研究至关重要 了解多个级别因素的相互作用（例如，表观遗传年龄的加速度，社会决定者此类 作为歧视和种族主义），造成症状伯恩的症状和该人群的健康差异。