Abstract

IntroductionDNA methylation studies have associated methylation levels at different CpG sites or genomic regions with lung function. Moreover, genetic ancestry has been associated with lung function in Latinos. However, no epigenome-wide association study (EWAS) of lung function has been performed in this population. Here, we aimed to identify DNA methylation patterns associated with lung function in pediatric asthma among Latinos.ResultsWe conducted an EWAS in whole blood from 250 Puerto Rican and 148 Mexican American children and young adults with asthma. A total of five CpGs exceeded the genome-wide significance threshold of p = 1.17 × 10−7 in the combined analyses from Puerto Ricans and Mexican Americans: cg06035600 (MAP3K6, p = 6.13 × 10−8) showed significant association with pre-bronchodilator Tiffeneau–Pinelli index, the probes cg00914963 (TBC1D16, p = 1.04 × 10−7), cg16405908 (MRGPRE, p = 2.05 × 10−8), and cg07428101 (MUC2, p = 5.02 × 10−9) were associated with post-bronchodilator forced vital capacity (FVC), and cg20515679 (KCNJ6) with post-bronchodilator Tiffeneau–Pinelli index (p = 1.13 × 10−8). However, these markers did not show significant associations in publicly available data from Europeans (p > 0.05). A methylation quantitative trait loci analysis revealed that methylation levels at these CpG sites were regulated by genetic variation in Latinos and the Biobank-based Integrative Omics Studies (BIOS) consortium. Additionally, two differentially methylated regions in REXOC and AURKC were associated with pre-bronchodilator Tiffeneau–Pinelli index (adjusted p < 0.05) in Puerto Ricans and Mexican Americans. Moreover, we replicated some of the previous differentially methylated signals associated with lung function in non-Latino populations.ConclusionsWe replicated previous associations of epigenetic markers with lung function in whole blood and identified novel population-specific associations shared among Latino subgroups.

Highlights

  • DNA methylation studies have associated methylation levels at different CpG sites or genomic regions with lung function

  • Puerto Ricans had lower pre- and post-Forced expiratory volume in 1 s (FEV1)% predicted and forced vital capacity (FVC) % predicted than Mexican Americans (p < 0.05), similar values were observed for the ­FEV1/FVC ratios

  • Exposure to second-hand smoking (SHS) and in utero maternal smoking was higher among individuals profiled with the Illumina Infinium HumanMethylation450 BeadChip array (450K) [17], compared with those where methylation was measured with the Illumina Infinium MethylationEPIC (EPIC)

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Summary

Introduction

DNA methylation studies have associated methylation levels at different CpG sites or genomic regions with lung function. Asthma is the most prevalent chronic inflammatory disorder among children and young adults worldwide [1]. It is characterized by reversible airflow obstruction and impaired lung function, with a larger decline in lung function among children and adults with asthma than in individuals without asthma [2]. Lung function is influenced by several factors, including smoking exposure, air pollution, socioeconomic factors, and prenatal exposures [8, 9]. These environmental factors can observably impact the epigenome

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