Estimating in silico causal effects of DNA methylation on gene expression through genetic anchors in airway epithelium in asthma
= 236) asthma. We conducted causal mediation analyses to assess whether DNAm affects gene expression or vice versa by using an adaptive bootstrap for the joint significance test to estimate causal effects for 38,562 eQTM pairs. DNAm is a plausible cause of gene expression in 73% of pairs. Genes in these eQTM pairs were significantly enriched in immune pathways and associated with asthma phenotypes. We replicated Expression Quantitative Trait Loci (eQTL) findings in various cell types in lung tissue and eQTL and Methylation Quantitative Trait Loci (meQTL) findings in the upper airway. These results suggest DNAm as a promising target for asthma prevention and therapy.
Authors
- Juan C. Celedón (ORCID: https://orcid.org/0000-0002-6139-5320)
- W C W Chen
- Ziyu Huang (ORCID: https://orcid.org/0000-0002-9062-1614)
- Soyeon Kim (ORCID: https://orcid.org/0000-0003-1573-2733)
- Hyun Jung Park (ORCID: https://orcid.org/0000-0002-8324-2624)
- Rebecca I. Caldino Bohn (ORCID: https://orcid.org/0009-0009-5584-8483)
Institutions
- University of Pittsburgh (US)
- UPMC Hillman Cancer Center (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-04-22
- DOI
- https://doi.org/10.1126/sciadv.ady3555
- Primary Topic
- Asthma and respiratory diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institute of Health Sciences
- National Science Foundation
- National Institutes of Health
- Center for Research Computing, University of Pittsburgh