Psychosocial experiences modulate asthma-associated genes through gene-environment interactions

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 251 children with asthma in Metro Detroit. 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. Importantly, we found 174 genes causally associated with asthma that are regulated by psychosocial factors, and 349 significant gene-environment interactions. These results demonstrate that social environments modulate the causal link between immune gene expression and asthma risk.

Functional dynamic genetic effects on gene regulation are specific to particular cell types and environmental conditions

“…In our study, since we compare ASE within the same genetic background, this limited sharing of ASE between treatments strongly suggests the existence of independent regulatory variants in context specific cis-regulatory modules. eQTL mapping consortia, like GTEx, identify eQTLs under one arbitrary condition, so genetic e↵ects on gene expression which occur only transiently during development or under certain environmental conditions will be missed [26,34,84,98,111,116]. A common approach to increasing identification of eQTLs is to increase the sample size.…”

Functional dynamic genetic effects on gene regulation are specific to particular cell types and environmental conditions

“…In our study, since we compare ASE within the same genetic background, this limited sharing of ASE between treatments strongly suggests the existence of independent regulatory variants in context specific cis-regulatory modules. eQTL mapping consortia, like GTEx, identify eQTLs under one arbitrary condition, so genetic effects on gene expression which occur only transiently during development or under certain environmental conditions will be missed [24,32,81,95,108,113]. A common approach to increasing identification of eQTLs is to increase the sample size.…”

Analysis of transcriptional changes in the immune system associated with pubertal development in a longitudinal cohort of children with asthma

“…5D and H) antigen-recognition proteins, with genetic effects on gene expression disappearing by late puberty. We had previously identified genotype-specific effects of lymphocyte and neutrophil fractions as well as nightly asthma symptoms on expression of TRBV30 in the same cohort 48 , which suggests that this association may be mediated by changes in blood cell composition that accompany puberty 49 . Interestingly, a sex-biased genetic effect on expression of TRBV30 had been previously reported 50 with a significant effect in adult male but not female spleen.…”

“…This gene encodes an enzyme catalyzing the inositol deacylation of glycosylphosphatidylinositol, which ensures proper folding of proteins involved in embryogenesis, neurogenesis, immunity, and fertilization 51 . Previously, we had found that expression of PGAP1 was modulated by the interaction with genotype across many environments including cell composition and cell composition and psychosocial factors, such as the extent of self-disclosure of thoughts and feelings, and frequency of verbal arguments within the family 48 . Lastly, we observed a strong effect of the T allele at rs28630791 on the expression of the nearby DSC1 gene only in mid-pubertal girls (Fig.…”