Psychosocial and Genetic Effects on Gene Expression and Asthma

心理社会和遗传对基因表达和哮喘的影响

• 批准号: 10391076
• 负责人: Francesca Luca
• 金额: $ 69.54万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10391076
• 关键词: Affect; African ancestry; Americas; Asthma; Behavior Therapy; Biological; Blood; Blood Cells; Cells; Cellular Immunity; Child; Child Health; Childhood; Chronic Disease; Complex; Data; Diagnosis; Disease; Emotional; Environment; Environmental Risk Factor; Family; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Transcription; Genetic Variation; Genotype; Glucocorticoids; Goals; Health; Hospitalization; Human; Hydrocortisone; Immune; Immunomodulators; Individual; Industrialization; Infection; Inflammatory; Leukocytes; Libraries; Measures; Mediating; Mediator of activation protein; Medical; Mitogens; Molecular; Outcome; Pathway interactions; Pattern; Peripheral; Peripheral Blood Mononuclear Cell; Personal Satisfaction; Phenotype; Population; Process; Psychosocial Factor; Resistance; Risk; Role; Sampling; Self Disclosure; Severities; Severity of illness; Siblings; Stimulus; Symptoms; Transcriptional Regulation; Treatment/Psychosocial Effects; Youth; asthmatic; base; cell type; cohort; design; experience; gene environment interaction; genetic association; genetic variant; genome-wide; immune function; immune health; inter-individual variation; metropolitan; physical conditioning; psychosocial; psychosocial resources; psychosocial stressors; pulmonary function; recruit; response; single cell analysis; single-cell RNA sequencing; social relationships; trait; transcriptome; transcriptome sequencing

Abstract In the past 8 years, we have studied a cohort of youth from metropolitan Detroit to investigate the effects of psychosocial stressors and resources on health, with a specific focus on asthma symptoms (Asthma in the Lives Of Families Today, ALOFT study). Our preliminary results from bulk RNA-seq analysis in peripheral leukocytes demonstrate that psychosocial factors are associated with transcriptional changes for a large number of genes, many of them involved in immunological functions. Importantly, we and others have uncovered an important role for blood cell type composition in inter-individual variation in response to psychosocial environments and their effects on immunological health and asthma symptoms. Here, we propose 1) to disentangle the contribution of psychosocial factors and asthmatic state on patterns of transcriptional dysregulation; 2) to investigate the effects of psychosocial factors on transcriptional regulation in blood cell type subpopulations; and 3) to determine the role of genetic variation in modulating these effects and their consequences for asthmatic children's health. To this end, we will use a combination of bulk and single cell RNA-sequencing on immune cells collected from children with asthma and their asymptomatic siblings. The complementary expertise of our team will uncover specific genetic and psychosocial factors associated with increased risk for poor physical health and wellbeing. These results will be important to design personalized medical and behavioral interventions to alleviate disease severity in children with asthma.

摘要 在过去的8年里，我们研究了底特律大都市的一群年轻人， 心理社会压力源和健康资源，特别关注哮喘症状（生活中的哮喘） 《今日家庭》，ALOFT研究）。我们在外周血白细胞中进行批量RNA-seq分析的初步结果 表明心理社会因素与大量基因的转录变化有关， 其中许多涉及免疫功能。重要的是，我们和其他人发现了一个重要的作用， 血细胞类型组成在个体间的变化，以响应心理社会环境和他们的 影响免疫健康和哮喘症状。在这里，我们建议1）解开的贡献 心理社会因素和哮喘状态对转录失调模式的影响; 2）探讨其影响 心理社会因素对血细胞类型亚群中转录调控的影响;以及3）确定 遗传变异在调节这些效应中的作用及其对哮喘儿童健康的影响。到 为此，我们将对从以下组织中收集的免疫细胞使用批量和单细胞RNA测序的组合： 哮喘儿童及其无症状的兄弟姐妹。我们团队的互补专业知识将揭示 与身体健康和福祉不良风险增加相关的特定遗传和心理社会因素。 这些结果将是重要的设计个性化的医疗和行为干预措施，以减轻疾病 儿童哮喘的严重程度。