Phenotypic and Molecular Signatures for Sleep Apnea and Related Morbidities

睡眠呼吸暂停及相关疾病的表型和分子特征

• 批准号: 10544494
• 负责人: Susan S. Redline
• 金额: $ 92.79万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10544494
• 关键词: Address; Adult; Affect; African American; Age; Anatomy; Apnea; Asian Americans; Big Data; Biological; Candidate Disease Gene; Cardiovascular system; Child; Clinical Data; Clinical Trials; Cognitive; Cohort Studies; Collaborations; Continuous Positive Airway Pressure; Data; Development; Diabetes Mellitus; Disease; Disease Outcome; Disease susceptibility; Environment; Environmental Risk Factor; Epidemiology; Ethnic Origin; Family; Functional disorder; Genetic; Genomics; Health; Healthcare; Heart failure; Hypertension; Individual; Individual Differences; Intervention; Laboratories; Leadership; Link; Measures; Medicine; Metabolic; Modernization; Molecular; Molecular Profiling; Morbidity - disease rate; Multicenter Studies; Outcome; Pathway interactions; Patients; Pattern; Phenotype; Physiological; Play; Polysomnography; Predisposition; Problem behavior; Race; Research Personnel; Resources; Risk; Risk Factors; Role; Severities; Severity of illness; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep Stages; Statistical Methods; Stents; Stroke; Technology; Translating; biobank; clinical care; data streams; disorder subtype; epidemiology study; experience; functional genomics; gene function; genetic variant; genome-wide analysis; genomic data; heritability pattern; improved; indexing; insight; multidisciplinary; non rapid eye movement; novel; patient subsets; personalized medicine; precision medicine; prediction algorithm; programs; respiratory; sex; social; trait

I have over 25 years of experience in sleep medicine epidemiological research and have played a leading role in studies that address the contributions of genetic, social and environmental risk factors to sleep disorders, the influences of sleep on health outcomes in children and adults, and the role of sleep interventions in improving health outcomes. My collaborators, mentees and I have identified that sleep apnea (SA) is highly prevalent, disproportionately affects Asians and African American children, and is associated with significantly increased risks for developing hypertension, stroke, heart failure, diabetes, and behavioral problems. We also have identified variability in these outcomes by sex, race/ethnicity, age, and genetic background. We have characterized the patterns of heritability for several SDB traits and through use of family-based and cohort studies (>20,000 individuals) have identified genome-wide significant associations for genetic variants in biological candidate genes, and sex- and sleep stage-specific analyses have provided insight into mechanisms that may explain the known sex and REM/NREM differences in SA severity. Despite this progress, however, the underlying molecular and physiological mechanisms for SA are not well understood, limiting both our ability to predict which patients with SA are most vulnerable to adverse health outcomes and our ability to develop treatments that reflect individual differences in SDB pathophysiology. Our emerging data suggest that these gaps may be overcome through systematic analysis of larger sets of polysomnography data, deriving more precise SDB phenotypes that reflect specific sleep and respiratory patterns, and linking these phenotypes to genomic and clinical data. Through leadership in multiple national consortia and multi-center studies we are poised to make transformative advances in understanding the phenotypic variability and genetics of sleep apnea and related traits. We plan to harness a critical mass of data, including those in the National Sleep Research Resource and genetic, genomic and clinical data available through several consortia, including the Trans- Omics in Precision Medicine and Partners HealthCare Biobank. We will expand our genetics/epidemiology team with leaders in sophisticated respiratory phenotyping, developing a multi-disciplinary program that will systematically extract quantitative metrics of SA phenotypes and link these to genetics, genomics, specific treatment responsiveness, and cardiovascular, metabolic and cognitive outcomes. Through collaborations with functional genomics laboratories, we will help identify functional genetic variants and clarify the function of genes and pathways associated with SA. We will use sophisticated statistical methods to derive and validate personalized medicine prediction algorithms based on these data streams. This enhanced biological understanding of SA will be translated into improved clinical care through better-informed clinical trials. Finally, we will create an environment that nurtures the development of new investigators equipped to use modern technologies and “big data” to identify signatures of disease susceptibility and outcomes.

我在睡眠医学流行病学研究方面拥有超过25年的经验并发挥了主导作用 在研究遗传、社会和环境风险因素对睡眠障碍的影响时， 睡眠对儿童和成人健康结果的影响，以及睡眠干预在改善健康方面的作用 我和我的合作者、学员发现睡眠呼吸暂停 (SA) 非常普遍， 不成比例地影响亚洲人和非裔美国儿童，并且与显着增加有关 我们还存在患高血压、中风、心力衰竭、糖尿病和行为问题的风险。 我们发现这些结果因性别、种族/民族、年龄和遗传背景而存在差异。 通过使用基于家庭和队列的方法，描述了几种 SDB 性状的遗传力模式 研究（超过 20,000 名个体）已经确定了基因组范围内遗传变异的显着关联 生物学候选基因以及性别和睡眠阶段特异性分析提供了对机制的深入了解 这或许可以解释 SA 严重程度中已知的性别和 REM/NREM 差异。 SA 的潜在分子和生理机制尚不清楚，限制了我们的能力 预测哪些 SA 患者最容易遭受不良健康结果以及我们发展的能力 我们的新数据表明，这些治疗反映了 SDB 病理生理学的个体差异。 通过对更大的多导睡眠图数据集进行系统分析，可以克服差距，得出更多 反映特定睡眠和呼吸模式的精确 SDB 表型，并将这些表型与 通过在多个国家联盟和多中心研究中的领导地位，我们正在 准备在了解睡眠呼吸暂停的表型变异性和遗传学方面取得变革性进展 我们计划利用大量数据，包括国家睡眠研究中的数据。 资源和遗传、基因组和临床数据可通过多个联盟获得，包括 Trans- 精准医学组学和合作伙伴医疗保健生物库我们将扩展我们的遗传学/流行病学。 与复杂呼吸表型分析领域的领导者合作，开发一个多学科计划， 自然地提取 SA 表型的定量指标，并将其与遗传学、基因组学、特定 通过与合作，治疗反应以及心血管、代谢和认知结果。 功能基因组实验室，我们将帮助识别功能遗传变异并阐明其功能 我们将使用复杂的统计方法来推导和验证与 SA 相关的基因和途径。 基于这些数据流的个性化医学预测算法增强了生物学功能。 对 SA 的了解将通过更明智的临床试验转化为改善的临床护理。 我们将创造一个环境，培养能够使用现代技术的新调查人员的发展 技术和“大数据”来识别疾病易感性和结果的特征。

项目成果

A Qualitative Assessment of the Acceptability of Smartphone Applications for Improving Sleep Behaviors in Low-Income and Minority Adolescents.

对智能手机应用程序改善低收入和少数族裔青少年睡眠行为的可接受性进行定性评估。

• 发表时间: 2019
• 影响因子: 3.1
• 作者: Quante, Mirja;Khandpur, Neha;Kontos, Emily Z;Bakker, Jessie P;Owens, Judith A;Redline, Susan
• 通讯作者: Redline, Susan

Sleep EEG spectral power is correlated with subjective-objective discrepancy of sleep onset latency in major depressive disorder.

睡眠脑电图频谱功率与重度抑郁症睡眠潜伏期的主客观差异相关。

• 发表时间: 2018-07-13
• 影响因子: 5.6
• 作者: Kang, Seung;Mariani, Sara;Marvin, Stephanie A;Ko, Kwang;Redline, Susan;Winkelman, John W
• 通讯作者: Winkelman, John W

Hypoxic burden captures sleep apnoea-specific nocturnal hypoxaemia.

缺氧负担指的是睡眠呼吸暂停特异性的夜间低氧血症。

• 发表时间: 2019
• 影响因子: 39.3
• 作者: Azarbarzin, Ali;Sands, Scott A;Taranto;Redline, Susan;Wellman, Andrew
• 通讯作者: Wellman, Andrew

Lung to finger circulation time in sleep study and coronary artery calcification: the Multi-Ethnic Study of Atherosclerosis.

睡眠研究中的肺到手指循环时间和冠状动脉钙化：动脉粥样硬化的多种族研究。

• 发表时间: 2020
• 影响因子: 4.8
• 作者: Kwon, Younghoon;Mariani, Sara;Reid, Michelle;Jacobs Jr, David;Lima, Joao;Kapur, Vishesh;Punjabi, Naresh;Redline, Susan
• 通讯作者: Redline, Susan

Infant sugar sweetened beverage and 100% juice consumption: Racial/ethnic differences and links with fathers' consumption in a longitudinal cohort.

婴儿％20糖％20甜％20饮料％20和％20100％％20果汁％20消费：％20种族/民族％20差异％20和％20链接％20与％20父亲％20消费％20在％20a％20纵向％20队列中。

• 发表时间: 2021-06
• 影响因子: 2.8
• 作者: Davison, K K;Franckle, R L;Lo, B K;Ash, T;Yu, X;Haneuse, S J;Redline, S;Taveras, E M
• 通讯作者: Taveras, E M