BMI trajectory in childhood is associated with asthma incidence at young adulthood mediated by DNA methylation

Rutu Rathod,Susan Ewart,S Hasan Arshad,Caroline Relton,Wilfried Karmaus,John W Holloway,Latha Kadalayil,Hongmei Zhang,Susan Ring

doi:10.1186/s13223-021-00575-w

Abstract

PurposeBody mass index (BMI) is associated with asthma but associations of BMI temporal patterns with asthma incidence are unclear. Previous studies suggest that DNA methylation (DNAm) is associated with asthma status and variation in DNAm is a consequence of BMI changes. This study assessed the direct and indirect (via DNAm) effects of BMI trajectories in childhood on asthma incidence at young adulthood.MethodsData from the Isle of Wight (IoW) birth cohort were included in the analyses. Group-based trajectory modelling was applied to infer latent BMI trajectories from ages 1 to 10 years. An R package, ttscreening, was applied to identify differentially methylated CpGs at age 10 years associated with BMI trajectories, stratified for sex. Logistic regressions were used to further exclude CpGs with DNAm at age 10 years not associated with asthma incidence at 18 years. CpGs discovered via path analyses that mediated the association of BMI trajectories with asthma incidence in the IoW cohort were further tested in an independent cohort, the Avon Longitudinal Study of Children and Parents (ALSPAC).ResultsTwo BMI trajectories (high vs. normal) were identified. Of the 442,474 CpG sites, DNAm at 159 CpGs in males and 212 in females were potentially associated with BMI trajectories. Assessment of their association with asthma incidence identified 9 CpGs in males and 6 CpGs in females. DNAm at 4 of these 15 CpGs showed statistically significant mediation effects (p-value < 0.05). At two of the 4 CpGs (cg23632109 and cg10817500), DNAm completely mediated the association (i.e., only statistically significant indirect effects were identified). In the ALSPAC cohort, at all four CpGs, the same direction of mediating effects were observed as those found in the IoW cohort, although statistically insignificant.ConclusionThe association of BMI trajectory in childhood with asthma incidence at young adulthood is possibly mediated by DNAm.

Highlights

The epidemic of obesity continues to increase globally despite its increasing awareness [1]
Path analyses Using path analyses, we explored the association between body mass index (BMI) trajectories at 1, 2, 4, 10 years and asthma incidence at 18 years, and whether the relationship between these variables was mediated by DNA methylation (DNAm) at 10 years (Fig. 1), with potential confounders included in each path
We estimated BMI trajectory based on data from subjects with BMI available for at least two time points

Summary

Introduction

The epidemic of obesity continues to increase globally despite its increasing awareness [1]. Obesity increases the risk of many chronic diseases among children and adults [1]. Asthma is a common chronic respiratory condition that predominantly originates in early childhood [2]. Rathod et al Allergy Asthma Clin Immunol (2021) 17:77 studies have identified obesity as a major risk factor for asthma [3]. A dose–response relationship of elevated body mass index (BMI) on asthma incidence has been demonstrated in a meta-analysis of prospective epidemiologic studies [4]. In the course of puberty, a gender reversal in asthma prevalence has been observed with a higher prevalence among boys before puberty and a higher prevalence among girls after puberty [5, 6]

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Results

Conclusion