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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的在过去的8年中，我们研究了来自底特律大都会的一群青年，以调查心理社会压力源和健康资源，特别关注哮喘症状（生活中的哮喘今天的家庭，高级研究）。我们的初步结果来自周围白细胞中的大量RNA-seq分析证明社会心理因素与大量基因的转录变化有关，其中许多参与免疫功能。重要的是，我们和其他人发现了重要的角色用于响应社会心理环境及其的血细胞类型组成对免疫健康和哮喘症状的影响。在这里，我们建议1）解开关于转录失调模式的社会心理因素和哮喘状态； 2）研究效果关于血细胞类型亚群中转录调控的心理社会因素； 3）确定遗传变异在调节这些作用及其对哮喘儿童健康的后果中的作用。到这一末端，我们将对从从患有哮喘的孩子及其无症状的兄弟姐妹。我们团队的完善专业知识将发现特定的遗传和社会心理因素与身体健康不良和福祉的风险增加有关。这些结果对于设计个性化的医学和行为干预措施以减轻疾病至关重要患有哮喘儿童的严重程度。