Abstract
BackgroundPrevious 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).ResultsIn 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).ConclusionPre-adolescence DNAm is associated with the change in BMI status from pre- to post-adolescence and such associations are likely to be gender-specific.
Highlights
Adolescence, marked by onset of physiologically normal puberty between the ages of 10 and 19, is a transition phase of growth and development between childhood and adulthood [1]
Assessment of body mass index (BMI) status transition at previously identified BMI‐associated CpGs Of the 187 CpGs associated with BMI in adults in the study of Wahl et al [16], 178 CpGs were available in the Isle of Wight (IoW) cohort
At 158 CpGs (88.8%), the associations of DNA methylation (DNAm) at age 10 years with BMI at 10 and 18 years in the IoW cohort had the same direction as those in Wahl et al [16], and at 64 of these CpGs [see Additional file 1], the associations were statistically significant at the 0.05 level
Summary
Adolescence, marked by onset of physiologically normal puberty between the ages of 10 and 19, is a transition phase of growth and development between childhood and adulthood [1]. Recent metaanalyses identified 187 CpG sites where DNAm was associated with BMI in adults [16] and 10 CpGs in children (age 2–10) and 1 CpG in adolescents (age 12–18) [17] All these studies focused on the association between DNAm and BMI cross-sectionally at a single time point. We hypothesized that at specific CpG sites, DNAm at an earlier age was associated with BMI status transition later in life. Previous studies have shown that DNA methylation (DNAm) is associated with body mass index (BMI). It is unknown whether DNAm at pre-adolescence is associated with BMI status transition from pre- to postadolescence. Findings in the IoW cohort were further tested in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC)
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