Sleep and Circadian Rhythms in Adolescence: Epigenetic Pathways of Cardiometabolic Risk

青春期的睡眠和昼夜节律：心脏代谢风险的表观遗传途径

• 批准号: 10439446
• 负责人: Erica Christine Jansen
• 金额: $ 13.79万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10439446
• 关键词: ARNTL gene; Achievement; Adolescence; Adolescent; Affect; Award; Behavioral; Biological; Biological Markers; Blood Pressure; Candidate Disease Gene; Cardiometabolic Disease; Characteristics; Chronic; Circadian Rhythms; Circadian desynchrony; Circadian gene expression; Cities; Clinical; Cohort Studies; Complex; Coupled; CpG dinucleotide; Cross-Sectional Studies; DNA Methylation; DNA Sequence; Data; Development; Environment; Epidemiologist; Epigenetic Process; Funding; Future; Gene Expression; Genes; Goals; Grant; Health; Heritability; High Prevalence; Hypertension; Inadequate Sleep Hygiene; Insulin Resistance; Intervention; Investigation; Knowledge; Laboratories; Lead; Leadership; Leukocytes; Link; Lipids; Longevity; Measurement; Measures; Mentors; Mentorship; Metabolic; Metabolic Diseases; Methylation; Mexico; Michigan; Modification; Molecular; Nutritional; Obesity; Observational Study; Outcome; Participant; Pathway interactions; Play; Population; Proxy; Puberty; Public Health; Public Health Schools; RORA gene; Research; Research Assistant; Research Design; Research Infrastructure; Resources; Risk; Risk Factors; Role; Schedule; Schools; Sleep; Sleep Deprivation; Sleep disturbances; Statistical Data Interpretation; Testing; Time; Training; United States National Institutes of Health; Universities; actigraphy; base; cardiometabolic risk; cardiometabolism; career; circadian; circadian biology; cohort; design; epidemiology study; epigenetic marker; epigenome; experience; flexibility; follow-up; improved; insight; methyl group; novel; nutrition; professor; prospective; puberty transition; skills; sleep pattern; therapy design

ABSTRACT Candidate: The PI is a Research Assistant Professor and nutritional epidemiologist whose primary career goal is to apply epigenetic approaches to improve the understanding of the interplay of sleep/circadian rhythms and nutrition on long-term cardiometabolic health risk. The proposed award includes a 5-year plan of training and research centered on circadian rhythms, epigenetics, study design, and skills required to lead a research team. Research context: Insufficient and mistimed sleep is recognized as a risk for adverse cardiometabolic outcomes. Adolescents are especially vulnerable as they have high prevalence of both short sleep duration and misaligned sleep timing. Yet, the unique contributions of sleep duration and circadian misalignment to cardiometabolic risk is unclear. Uncovering the epigenetic mechanisms behind these relationships is a highly promising avenue for this public health issue. Recent cross-sectional evidence shows that epigenetic alterations of metabolic and circadian genes might play an intermediary role in the relationships between sleep/circadian rhythms and cardiometabolic health, yet longitudinal investigations are scarce. The application of epigenetic approaches to identify potential mechanisms that link sleep to cardiometabolic health is novel. Research Objectives: The aims are two-fold: 1) to evaluate the independent associations of sleep duration and timing with cardiometabolic health among adolescents and 2) to examine epigenetic associations between insufficient/mistimed sleep and cardiometabolic health. Research Plan: The PI will analyze existing data from an NIH-funded established cohort study of adolescents in Mexico City with highly variable sleep patterns (some participants' sleep patterns are constrained by morning school shifts while others have more flexibility due to an afternoon school shift). Associations between objectively collected sleep data (7-days of actigraphy) and cardiometabolic biomarkers (adiposity, blood pressure, and insulin resistance collected at two time points 24 months apart) will be analyzed. Stored leukocytes will be used to measure gene expression and epigenome-wide DNA methylation. Longitudinal and epigenome-wide statistical analyses will be conducted. Career Goals and Development: The PI will gain expertise in assessment of circadian rhythms, epigenetics laboratory investigation, and epidemiological study design through didactic and hands-on experiences. She will also advance in her leadership, mentorship, and grantsmanship skills, and by the end of the training period will apply for an R01 centered on sleep/circadian rhythms, nutrition, and epigenetics. Environment: Resources available to the PI include a well-rounded and supportive team of mentors representing the fields of sleep/circadian rhythms, epigenetics, nutrition and cardiometabolic health; and the excellent research infrastructure at the University of Michigan School of Public Health where the PI has been guaranteed 80% of time devoted to the research goals delineated in the proposal.

抽象的 候选人：PI是研究助理教授和营养流行病学家，其主要职业目标 是采用表观遗传方法来提高对睡眠/昼夜节律和 长期心脏代谢健康风险的营养。拟议的裁决包括一项5年的培训计划和 研究集中在领导研究团队所需的昼夜节律，表观遗传学，研究设计和技能上。 研究环境：不足和丧失的睡眠被认为是不良心脏代谢的风险 结果。青少年特别容易受到伤害，因为他们的睡眠时间很高 和错位的睡眠时间。然而，睡眠持续时间和昼夜节律的独特贡献对 心脏代谢风险尚不清楚。揭示这些关系背后的表观遗传机制是高度的 这个公共卫生问题有希望的途径。最近的横截面证据表明表观遗传 代谢和昼夜节律基因的改变可能在中间角色中起作用 睡眠/昼夜节律和心脏代谢健康，但纵向研究却很少。应用程序 鉴定将睡眠与心脏代谢健康联系起来的潜在机制的表观遗传学方法是新颖的。 研究目标：目的是两个方面：1）评估睡眠持续时间的独立关联 以及青少年心脏代谢健康的时间和2）检查表观遗传关联 睡眠不足/不足的睡眠和心脏代谢健康。 研究计划：PI将从NIH资助的青少年研究中分析现有数据 在墨西哥城的睡眠方式高度可变（某些参与者的睡眠方式受到限制 晨间学校的变化，而其他人则由于下午的学校轮班而具有更大的灵活性。之间的关联 客观收集的睡眠数据（Actiraphy的7天）和心脏代谢生物标志物（肥胖，血液 将分析压力和在相隔24个月的两个时间点收集的胰岛素抵抗）。存储 白细胞将用于测量基因表达和表观基因组范围的DNA甲基化。纵向和 将进行全依性基因组全统计分析。 职业目标和发展：PI将获得评估昼夜节律，表观遗传学的专业知识 实验室调查以及通过教学和动手经验设计的流行病学研究。她会的 还晋升了她的领导，指导和授予技巧，到培训期结束时 申请以睡眠/昼夜节律，营养和表观遗传学为中心的R01。 环境：PI可用的资源包括一个全面且支持的导师团队 代表睡眠/昼夜节律，表观遗传学，营养和心脏代谢健康的领域；和 密歇根大学公共卫生学院的优秀研究基础设施 保证80％的时间用于提案中描述的研究目标。