An epigenome-wide association study of child appetitive traits and DNA methylation.

Holly A Harris, Chloe Friedman, Anne P Starling, Dana Dabelea, Susan L Johnson, Bernard F Fuemmeler, Dereje Jima, Susan K Murphy, Cathrine Hoyo, Pauline W Jansen, Janine F Felix, Rosa H Mulder

Journal: Appetite 2024;191():107086

PMID: 37844693

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Abstract

The etiology of childhood appetitive traits is poorly understood. Early-life epigenetic processes may be involved in the developmental programming of appetite regulation in childhood. One such process is DNA methylation (DNAm), whereby a methyl group is added to a specific part of DNA, where a cytosine base is next to a guanine base, a CpG site. We meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R Study (n = 1,086, Rotterdam, the Netherlands) and the Healthy Start study (n = 236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their child's food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Children's Eating Behaviour Questionnaire at age 4-5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait when examining individual CpG-sites. However, when examining multiple CpGs jointly in so-called differentially methylated regions, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of these behaviors.

Address: Department of Child & Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Erasmus University Rotterdam, Department of Psychology, Education & Child Studies, Rotterdam, the Netherlands. Electronic address: [email protected].; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: [email protected].; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: [email protected].; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: [email protected].; Department of Pediatrics, Section of Nutrition, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: [email protected].; Virginia Commonwealth University, Massey Comprehensive Cancer Center, Richmond, VA, USA. Electronic address: [email protected].; Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA; Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA. Electronic address: [email protected].; Duke University Medical Center, Department of Obstetrics and Gynecology, Reproductive Sciences, Durham, NC, USA. Electronic address: [email protected].; Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA. Electronic address: [email protected].; Department of Child & Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Erasmus University Rotterdam, Department of Psychology, Education & Child Studies, Rotterdam, the Netherlands. Electronic address: [email protected].; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address: [email protected].; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address: [email protected].

DOI: 10.1016/j.appet.2023.107086

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MeSH Terms: Child, Preschool, Humans, Appetite, Appetite Regulation, Appetitive Behavior, CpG Islands, DNA Methylation, Epigenesis, Genetic, Epigenome, Feeding Behavior, Fetal Blood, Genome-Wide Association Study, Netherlands, Satiation