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 Mulder

doi:10.1101/2023.07.17.549289

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

bioRxiv [Preprint]. 2023 Jul 18:2023.07.17.549289. doi: 10.1101/2023.07.17.549289.

Authors

Holly A Harris^{1

2

3}, Chloe Friedman^{4

5}, Anne P Starling^{4

5

6}, Dana Dabelea^{4

5

7}, Susan L Johnson⁸, Bernard F Fuemmeler⁹, Dereje Jima^{10

11}, Susan K Murphy¹², Cathrine Hoyo¹³, Pauline W Jansen^{1

2

3}, Janine F Felix^{2

14}, Rosa Mulder^{2

14}

Affiliations

¹ Department of Child & Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
² The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
³ Erasmus University Rotterdam, Department of Psychology, Education & Child Studies, Rotterdam, the Netherlands.
⁴ Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁵ Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁶ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁷ Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁸ Department of Pediatrics, Section of Nutrition, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁹ Virginia Commonwealth University, Mase Comprehensive Cancer Center, Richmond, VA, USA.
¹⁰ Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA.
¹¹ Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.
¹² Duke University Medical Center, Department of Obstetrics and Gynecology, Reproductive Sciences, Durham, NC, USA.
¹³ Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.
¹⁴ Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Abstract

Childhood appetitive traits are consistently associated with obesity risk, and yet their etiology is poorly understood. Appetitive traits are complex phenotypes which are hypothesized to be influenced by both genetic and environmental factors, as well as their interactions. Early-life epigenetic processes, such as DNA methylation (DNAm), may be involved in the developmental programming of appetite regulation in childhood. In the current study, 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 at the individual site-level. However, at the regional level, 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.

Keywords: Appetitive traits; DNA methylation; Epigenome-wide association study; childhood; eating behaviors; epigenetics.

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Preprint

Abstract

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