BMI trajectory in childhood is associated with asthma incidence at young adulthood mediated by DNA methylation
Year: 2021
Type: article
Study design: Observational Study
Abstract: PURPOSE: Body 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. METHODS: Data 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). RESULTS: Two 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. CONCLUSION: The association of BMI trajectory in childhood with asthma incidence at young adulthood is possibly mediated by DNAm.
Institutions: University of Memphis, Michigan State University, University of Southampton, University Hospitals Bristol NHS Foundation Trust, University of Bristol, MRC Integrative Epidemiology Unit, University Hospital Southampton NHS Foundation Trust, NIHR Southampton Biomedical Research Centre, David Hide Asthma and Allergy Research Centre
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,590
Funders: Wellcome Trust, University of Memphis, Asthma and Lung UK, University of Bristol, National Institutes of Health, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases
Awards: G1415860003, G149876332, G1684393010, G1793884970, G1955001954, G235045266, Does epigenetic methylation explain the gender-switch in adolescent asthma?, G317400622, G3233603352, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G3987754321, Accessible resource for integrated epigenomics studies (ARIES), G4807506537, G5001017760, G5107313190, G5192599444, G5313676757, Accessible resource for integrated epigenomics studies (ARIES), G6119919417, G6689231961, G6751436026, G6940952066, G7039346749, Transgenerational epigenetic inheritance of allergy in a multigenerational cohort, G738105237, G7775523268, G801210579, Epidemiology of asthma: risk and prognosis in a cohort from birth to adolescence, G8437369045, G8459925867, G8782766175, G9000164307
OpenAlex ID: W3158974797