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Social interactions and the overall psychosocial environment have a demonstrated impact on health, particularly for people living in disadvantaged urban areas. The growing field of social genomics investigates how various dimensions of a person's social and psychological environment influence gene expression. However, very few eQTL studies in humans have included comprehensive information on psychosocial exposures. Through the Asthma in the Lives Of Families Today (ALOFT) project we investigated the effects of psychosocial experiences on gene expression in peripheral blood immune cells of 251 children with asthma living in Metro Detroit. We considered psychosocial experiences spanning three major axes: socioeconomic status, social relationships and emotionality. Using RNA-sequencing and a new machine learning approach we identified transcriptional signatures of 20 variables including psychosocial factors, blood cell composition and asthma symptoms. Using additional longitudinal data we show significant correlation between longitudinal change in observed variables and their transcriptional signatures. To explore potential molecular pathways linking psychosocial experiences and asthma symptoms, we considered overlaps between transcriptional signatures of psychosocial, blood and asthma variables. For example, psychosocial measures of self-disclosure, maternal responsiveness, and socioeconomic status were associated with forced expiratory volume. Mediation analysis indicated a likely causal connection between self-disclosure and forced expiratory volume that is partially explained by blood cell composition. Importantly, we found 98 genes causally associated with asthma that are regulated by psychosocial factors (e.g. socioeconomic status, maternal responsiveness, family conflict), and 349 significant gene-environment interactions across 136 unique genes. We found that the majority of our GxE genes replicated in other datasets of GxE in gene expression, including in response to chemical treatments, pathogens and cell type composition. To illustrate the potential impact of GxE, we showed that A allele at rs12922757 increases the expression of the Growth Arrest Specific 8 gene (GAS8) only in individuals with perceived high socio-economic status (GxE). Lower expression of GAS8 has been associated with increased risk of asthma. Our results demonstrate that social environments modulate the causal link between immune gene expression and asthma risk.