Pre-adolescence DNA methylation is associated with BMI status change from pre- to post-adolescence

Jiajing Wang, Hongmei Zhang, Faisal I Rezwan, Caroline Relton, S Hasan Arshad, John W Holloway

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BACKGROUND: Previous studies have shown that DNA methylation (DNAm) is associated with body mass index (BMI). However, it is unknown whether DNAm at pre-adolescence is associated with BMI status transition from pre- to post-adolescence. In the Isle of Wight (IoW) birth cohort, genome-wide DNA methylation in whole blood was measured using Illumina Infinium Human450 and EPIC BeadChip arrays in n = 325 subjects, and pre- to post-adolescence BMI transition was classified into four groups: (1) normal to normal, (2) normal to overweight or obese, (3) overweight or obese to normal, and (4) persistent overweight or obese. We used recursive random forest to screen genome-wide Cytosine-phosphate-Guanine (CpG) sites with DNAm potentially associated with BMI transition for each gender, and the association of BMI status transition with DNAm at an earlier age was assessed via logistic regressions. To evaluate gender specificity, interactions between DNAm and gender were included in the model. Findings in the IoW cohort were further tested in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC).

RESULTS: In total, 174 candidate CpGs were selected including CpGs from screening and CpGs previously associated correctionally with BMI in children and adults. Of these 174 CpGs, pre-adolescent DNAm of 38 CpGs in the IoW cohort was associated with BMI status transition, including 30 CpGs showing gender-specific associations. Thirteen CpGs showed consistent associations between the IoW cohort and the ALSPAC cohort (11 of which were gender-specific).

CONCLUSION: Pre-adolescence DNAm is associated with the change in BMI status from pre- to post-adolescence and such associations are likely to be gender-specific.

Original languageEnglish
Article number64
Number of pages11
JournalClinical epigenetics
Issue number1
Early online date25 Mar 2021
Publication statusPublished - 01 Dec 2021
Externally publishedYes


  • Adolescence
  • BMI status transition
  • Body mass index (BMI)
  • DNA methylation
  • Longitudinal
  • Obesity
  • Age Factors
  • Epigenesis, Genetic
  • Humans
  • Child, Preschool
  • DNA Methylation/genetics
  • Infant
  • Male
  • Adolescent Development
  • Obesity/genetics
  • Young Adult
  • Adult
  • Female
  • Child
  • Body Mass Index
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • United Kingdom
  • Adolescent
  • Longitudinal Studies
  • Cohort Studies


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