Abstract
Social interactions and the overall psychosocial environment have a demonstrated impact on health, particularly for people living in disadvantaged urban areas. Here, we investigated the effect of psychosocial experiences on gene expression in peripheral blood immune cells of children with asthma in Metro Detroit. Using RNA-sequencing and a new machine learning approach, we identified transcriptional signatures of 19 variables including psychosocial factors, blood cell composition, and asthma symptoms. Importantly, we found 169 genes associated with asthma or allergic disease that are regulated by psychosocial factors and 344 significant gene-environment interactions for gene expression levels. These results demonstrate that immune gene expression mediates the link between negative psychosocial experiences and asthma risk.
Highlights
Psychosocial experiences have long been recognized to affect human health (Miller et al, 2009)
To denoise and impute psychosocial effects on gene expression for the entire cohort of 251 participants, we developed a new machine learning approach based on generalized linear models with elastic net regularization (GLMnet; Friedman et al, 2010) and cross-validation
We collected a unique dataset with genome-wide gene expression paired with extensive and accurate assessment of each participant’s biological and psychosocial functioning, across a variety of domains known or likely to be relevant for asthma
Summary
Psychosocial experiences have long been recognized to affect human health (Miller et al, 2009). Asthma is a chronic inflammatory disease of the respiratory tract that disproportionately affects children (Moorman et al, 2012). It is one of the costliest pediatric health conditions (Weiss et al, 2000) and a leading cause of school absenteeism (Akinbami and Centers for Disease Control and Prevention National Center for Health Statistics, 2006). Struggling cities, such as Detroit, are at an especially high risk for asthma morbidity and mortality (Sullivan et al, 2002).
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