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

Abstract

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.

Blood-based genome-wide DNA methylation correlations across body fat and adiposity-related biochemical traits

“…We also found evidence for a probe-by-sex interaction with DNAm at probe cg12269535 located in the SRF gene, which is associated with insulin resistance and may contribute to the pathogenesis of Type 2 Diabetes [34]. We note that probe-by-sex interactions have been previously investigated in the context of BMI [4, 35], with each study identifying only a single CpG, however we were unable to replicate any previous findings (Supplementary Figure 5).…”

Considerations on efforts needed to improve our understanding of the genetics of obesity

“…Histone modifications, such as acetylation and methylation, are also associated with BMI, both globally and at specific gene promoter levels [35,36]. While these epigenetic changes are generally viewed as consequences, rather than causes, of excess adiposity [33,37], opposing viewpoints have been proposed [38,39]. Associations of non-coding RNAs, such as microRNAs and lincRNAs, with obesity have also been observed [40][41][42].…”

Recent progress in epigenetics of obesity

“…Furthermore, a total of 174 candidate CpG loci from whole blood DNAm of 325 subjects were screened, which also included correction loci previously found to be associated with BMI in children and adults. Of these 174 CpG loci, 38 CpG loci in prepubertal DNAm were associated with shifts in BMI status, including 30 CpG loci that were sex-specific [ 30 ]. Prepubertal DNAm was associated with changes in BMI status during pubertal development, and these associations may be gender-specific.…”