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: 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
• 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

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 患有镰状细胞病（SCD）的个体经历有害的心理神经症状，如疼痛， 睡眠障碍、抑郁症状和认知障碍。在这些症状中， 个体间变异很少有研究试图调查为什么有些人的经历更糟 精神神经症状更明显确定生物因素，如表观遗传机制， 影响SCD症状体验的变异性，可以帮助为风险评估的发展提供信息 工具和干预措施，促进健康维护，生活质量，并减少这方面的健康差距， 人口最近的证据表明，一个人的表观遗传年龄可能与 SCD的精神神经症状经历。通过评估DNA甲基化来计算表观遗传年龄 在许多CpG位点的模式，占细胞老化或下降的组织功能的步伐。 过早的表观遗传年龄加速性脓疱病涉及许多生理过程，包括增加 炎症、氧化应激和线粒体功能障碍。表观遗传年龄加速 和精神神经症状的经验，在其他慢性疾病人群最近已被 鉴定然而，表观遗传性年龄加速是否发生，以及它是否与这些症状有关， 患有SCD的人仍然未知。这项横断面研究的具体目的是：1）描述 表观遗传衰老DNA甲基化模式，并确定表观遗传衰老加速的存在，以及2） 确定表观遗传年龄加速和心理神经症状（疼痛、睡眠）之间的关联 障碍、抑郁症状和认知功能）。DNA样本和病人- 作为镰状细胞病联盟的一部分，杜克大学已经收集了报告的结局数据 本研究将使用研究登记研究（n=92）。DNA甲基化数据将从提取的 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了 表观遗传老化的不同措施和特征，表观遗传年龄加速将使用 三个表观遗传时钟（Horvath，Hannum和Levine）。我们还将研究是否计算从 每个时钟在样本中是相关的。存在的每种关注症状的患者报告数据 SCDIC登记将用于确定与表观遗传年龄加速的关联， 表观遗传时钟这项“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， 人口所生成的数据对于设计严格和充分把握度的R 01研究至关重要， 了解多个层面因素的相互作用（例如，表观遗传年龄加速，社会决定因素， 歧视和种族主义），导致这一人群的症状负担和健康差异。