DNA Methylation and Asthma Acquisition during Adolescence and Post-Adolescence, an Epigenome-Wide Longitudinal Study.

Aniruddha Rathod,Wilfried Karmaus,Syed Hasan Arshad,Caroline L Relton,Hongmei Zhang,Susan Ewart,John W Holloway

doi:10.3390/jpm12020202

Abstract

The role of epigenetics in the pathogenesis of asthma acquisition in adolescence and post-adolescence has been unknown. We carried out a longitudinal epigenome-wide association study, using data from the Isle of Wight Birth Cohort (IOWBC). To improve statistical power, we first screened CpGs based on associations of DNA methylation (DNAm) at an age of 10 years (pre-adolescence) with asthma acquisition at 10–18 years (during adolescence). A logistic regression with repeated measures was applied to CpGs that passed screening to examine the associations of pre-adolescence DNAm with asthma acquisition from 10–18 years and 18–26 years, with an interaction term to evaluate transition period specificity. Findings were further tested in an independent birth cohort, ALSPAC. In total, 205 CpGs (with 150 being females) showed associations with asthma acquisition (main or interaction effects) at FDR = 0.05 in IOWBC, of which 112 (90 being females) showed consistent associations in the ALSPAC. Genes that the identified CpGs were mapped to, e.g., AKAP1 and ENO1, have been shown to be associated with the risk of asthma. Our findings indicated that DNAm at specific CpGs was associated with asthma acquisition. CpGs showing such associations were likely to be different between males and females and, at certain CpGs, were unique to a specific transition period.

Highlights

Since our study focused on asthma acquisition starting from the age of 10 years in the Isle of Wight Birth Cohort (IOWBC), subjects with asthma at four years were excluded
We assessed the longitudinal association of DNA methylation (DNAm) measured at earlier ages with asthma acquisition at later ages for each sex based on data from two independent cohorts, with the IOWBC as the discovery cohort and the Avon Longitudinal Study of Parents and Children (ALSPAC) as the replication cohort
In the IOWBC, at 205 CpGs, pre-adolescence DNAm was shown to be associated with the odds of asthma acquisition from pre- to post-adolescence, and post-adolescence DNAm was associated with asthma acquisition from post-adolescence to adulthood

Summary

Introduction

Asthma is the most prevalent chronic respiratory condition [1], affecting 1–18% of the population in several countries [2]. Childhood asthma has become a major public health issue [3], with an increasing prevalence worldwide [4]. Environmental factors such as air pollution, infectious agents, and tobacco smoke have been shown to be associated with the development of asthma [5]. Recent studies suggest that DNAm signatures of cytosine-phosphate-guanines (CpG) sites are associated with asthma [7–9]. Since peripheral blood is readily obtainable and easy to handle in laboratory processing, and information of immune cells in blood is relevant to asthma pathogenesis [10], DNAm in peripheral blood cells has been commonly examined in epigenome-wide studies of asthma [11–14]

Methods

Results

Conclusion