Estimating in-silico causal effects of DNA methylation on gene expression through genetic anchors in airway epithelium from youth with and without asthma

Expression quantitative trait methylation (eQTM) analyses have identified numerous associations between DNA methylation (DNAm) and gene expression, but the causal pathways underlying such associations remain poorly understood. Using SNPs as genetic anchors, we examined potential causal effects between DNAm and gene expression in cis- and trans-associations in nasal epithelial samples from youth with (n=219) and without (n=236) asthma. We conducted causal mediation analyses to assess whether DNA methylation affects gene expression or vice versa, by employing 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 eQTL findings in various cell types in lung tissue and eQTL and meQTL findings in upper airway. These results suggest DNAm as a promising target ..., All data shared in this repository consist of summary-level statistics and do not contain any individual-level or directly identifiable participant information. The reported results are aggregated across participants and include only statistical measures, thereby minimizing the risk of re-identification.
The human samples were derived from the Epigenetic Variation and Childhood Asthma in Puerto Ricans (EVA-PR) study, which was approved by the institutional review boards of the University of Puerto Rico (Protocol #0160713) and the University of Pittsburgh (Protocol #20050135).  Written parental consent and assent were obtained from participants younger than 18 years, and written consent was obtained from participants 18 years or older. , Epigenetic Variation and Childhood Asthma in Puerto Ricans Study (EVA-PR) is a case-control study of asthma in subjects aged 9 to 20 years [1]. From February 2014 through May 2017, 543 subjects with (cases, n=269) and without (controls, n=274) asthma were recruited from households in the metropolitan area of San Juan (Puerto Rico) using a multistage probability sampling design. The study protocol included questionnaires on respiratory health, measurement of serum allergen-specific IgEs, and collection of nasal epithelial samples for DNA and RNA extraction.
Asthma was defined as physician-diagnosed asthma and wheeze in the previous year. Control subjects had neither physician-diagnosed asthma nor wheeze in the previous year. Levels of IgEs specific to common allergens were measured in serum using the UniCAP 100 system (Pharmacia & Upjohn, Kalamazoo, MI). For each allergen, an IgE ≥0·35 IU/mL was considered positive. Atopy was defined as having at least one positive specific IgE test ..., # Data from: Estimating in-silico causal effects of DNA methylation on gene expression through genetic anchors in airway epithelium from youth with and without asthma

Dataset DOI: [10.5061/dryad.rxwdbrvpq](https://doi.org/10.5061/dryad.rxwdbrvpq)

## Description of the data and file structure

The study used a subset of the participants from the Epigenetic Variation and Childhood Asthma in Puerto Ricans Study (EVA-PR), originally designed to study methylation profiles associated with atopy in asthmatic children [1]. 

In the current study, we employed Expression Quantitative Trait Methylation (eQTM), Expression Quantitative Trait Locus (eQTL), and Methylation Quantitative Trait Locus (meQTL) analyses to identify potential causal relationships between DNA methylation and gene expression in pediatric asthma, using SNPs as genetic anchors. We tested both cis- and trans-associations and replicated our cis-eQTL and cis-meQTL results with those previouly reported in Soliai et al[2].

1- E. F...,