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

  1. Justyna A Resztak
  2. Allison K Farrell
  3. Henriette Mair-Meijers
  4. Adnan Alazizi
  5. Xiaoquan Wen
  6. Derek E Wildman
  7. Samuele Zilioli
  8. Richard B Slatcher
  9. Roger Pique-Regi  Is a corresponding author
  10. Francesca Luca  Is a corresponding author
  1. Wayne State University, United States
  2. Miami University, United States
  3. University of Michigan, United States
  4. University of South Florida, United States

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.

Data availability

The data are available on dbGAP. Accession number: phs002182.v1.p1.

The following data sets were generated

Article and author information

Author details

  1. Justyna A Resztak

    Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Allison K Farrell

    Department of Psychology, Miami University, Oxford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Henriette Mair-Meijers

    Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Adnan Alazizi

    Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Xiaoquan Wen

    University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Derek E Wildman

    College of Public Health, University of South Florida, Tampa, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Samuele Zilioli

    Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Richard B Slatcher

    Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Roger Pique-Regi

    Wayne State University, Detroit, United States
    For correspondence
    rpique@wayne.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1262-2275
  10. Francesca Luca

    Wayne State University, Detroit, United States
    For correspondence
    fluca@wayne.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8252-9052

Funding

National Heart, Lung, and Blood Institute (R01HL114097)

  • Samuele Zilioli
  • Richard B Slatcher

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Participants were included from an ongoing longitudinal study, Asthma in the Lives of Families Today (ALOFT; recruited from November 2010-July 2018, Wayne State University Institutional Review Board approval #0412110B3F).

Copyright

© 2021, Resztak et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,559
    views
  • 144
    downloads
  • 15
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Justyna A Resztak
  2. Allison K Farrell
  3. Henriette Mair-Meijers
  4. Adnan Alazizi
  5. Xiaoquan Wen
  6. Derek E Wildman
  7. Samuele Zilioli
  8. Richard B Slatcher
  9. Roger Pique-Regi
  10. Francesca Luca
(2021)
Psychosocial experiences modulate asthma-associated genes through gene-environment interactions
eLife 10:e63852.
https://doi.org/10.7554/eLife.63852

Share this article

https://doi.org/10.7554/eLife.63852

Further reading

    1. Genetics and Genomics
    2. Neuroscience
    Thomas P Spargo, Lachlan Gilchrist ... Alfredo Iacoangeli
    Research Article

    Continued methodological advances have enabled numerous statistical approaches for the analysis of summary statistics from genome-wide association studies. Genetic correlation analysis within specific regions enables a new strategy for identifying pleiotropy. Genomic regions with significant ‘local’ genetic correlations can be investigated further using state-of-the-art methodologies for statistical fine-mapping and variant colocalisation. We explored the utility of a genome-wide local genetic correlation analysis approach for identifying genetic overlaps between the candidate neuropsychiatric disorders, Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Parkinson’s disease, and schizophrenia. The correlation analysis identified several associations between traits, the majority of which were loci in the human leukocyte antigen region. Colocalisation analysis suggested that disease-implicated variants in these loci often differ between traits and, in one locus, indicated a shared causal variant between ALS and AD. Our study identified candidate loci that might play a role in multiple neuropsychiatric diseases and suggested the role of distinct mechanisms across diseases despite shared loci. The fine-mapping and colocalisation analysis protocol designed for this study has been implemented in a flexible analysis pipeline that produces HTML reports and is available at: https://github.com/ThomasPSpargo/COLOC-reporter.

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics
    Arkadiy K Golov, Alexey A Gavrilov ... Sergey V Razin
    Research Article

    The enhancer-promoter looping model, in which enhancers activate their target genes via physical contact, has long dominated the field of gene regulation. However, the ubiquity of this model has been questioned due to evidence of alternative mechanisms and the lack of its systematic validation, primarily owing to the absence of suitable experimental techniques. In this study, we present a new MNase-based proximity ligation method called MChIP-C, allowing for the measurement of protein-mediated chromatin interactions at single-nucleosome resolution on a genome-wide scale. By applying MChIP-C to study H3K4me3 promoter-centered interactions in K562 cells, we found that it had greatly improved resolution and sensitivity compared to restriction endonuclease-based C-methods. This allowed us to identify EP300 histone acetyltransferase and the SWI/SNF remodeling complex as potential candidates for establishing and/or maintaining enhancer-promoter interactions. Finally, leveraging data from published CRISPRi screens, we found that most functionally verified enhancers do physically interact with their cognate promoters, supporting the enhancer-promoter looping model.