Psychosocial and Genetic Effects on Gene Expression and Asthma

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.