Researchers identify master regulator genes of asthma
Published: August 19, 2020
Asthma is a chronic respiratory disease that affects millions of people worldwide of all ages. Despite much that is known about asthma, much remains unknown, and people continue to suffer with poorly controlled or undiagnosed asthma. Study of all of the genes that are expressed (i.e. transcriptomics) in the airway can uncover new information about the processes underlying asthma. Because asthma affects the entire airway, nasal transcriptomics can provide a valuable window into asthma pathophysiology that is accessible without an invasive procedure. Although nasally expressed genes have been linked to asthma, causal relationships among the genes and biological processes identified have been more difficult to disentangle.
In a recently published study in The Journal of Allergy and Clinical Immunology (JACI), a multi-institutional team led by investigators from the Icahn School of Medicine at Mount Sinai report their identification of master regulator genes of asthma. Do et al. studied nasal samples from multiple cohorts of children and adults with asthma and healthy controls. They examined genes expressed in these nasal samples using nasal transcriptomics to find gene signatures for severe persistent asthma and mild/moderate persistent asthma. To investigate the biological context of the identified asthma genes, they applied network-based analyses to uncover biologic processes for the asthma gene signatures. The team then used probabilistic causal methods to identify master regulator genes statistically inferred to causally regulate the expression of genes associated with severe persistent asthma, mild/moderate persistent asthma, and asthma across severity and ages. The researchers validated their findings in two independent test cohorts.
Nasal gene signatures for severe persistent asthma and mild/moderate persistent asthma were identified and both found to be enriched in co-expression network modules for ciliary function and inflammatory response. By applying probabilistic causal methods to these gene signatures and validation testing in independent cohorts, the researchers identified (1) a master regulator gene common to asthma across severity and ages (FOXJ1); (2) master regulator genes of severe persistent asthma in children (LRRC23, TMEM231, CAPS, PTPRC FYB); and (3) master regulator genes of mild/moderate persistent asthma in children and adults (C1orf38, FMNL1). The identified master regulators are statistically inferred to causally regulate the expression of downstream genes that modulate ciliary function and inflammatory response to influence asthma.
Network study of nasal transcriptome profiles from multiple human cohorts identified nasal gene signatures for severe persistent asthma, mild/moderate persistent asthma, and master regulator genes of asthma. The identified master regulator genes of asthma provide a novel path forward to further uncovering asthma mechanisms and therapy.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.
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