Oral Presentation Australian & New Zealand Obesity Society 2014 Annual Scientific Meeting

Genome wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood. (#69)

Rae-Chi Huang 1 , Liz Davis 1 2 , Emma S Garratt 3 , Hong Pan 4 , Y Wu 4 , Sheila J Barton 3 , Graham C Burdge 3 , Keith M Godfrey 3 , Joanna D Holbrook 4 , Karen A Lillycrop 3
  1. Telethon Kids Institute, University of Western Australia, Perth, WA, Australia
  2. Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, WA, Australia
  3. University of Southampton, Southampton, United Kingdom
  4. Singapore Institute for Clinical Sciences, Singapore

Introduction: Childhood obesity is a major public health issue. Here we investigated whether differential methylation was associated with morbid childhood obesity.

Methods: We studied methylation profiles in whole blood from 79 morbidly obese children (mean BMI z-score 2.6) and 71 age/sex matched controls (mean BMI z-score 0.1). The morbidly obese children were derived from a tertiary clinical referral centre at Princess Margaret Hospital, Perth.  Controls were recruited from schools.  DNA samples from the obese subjects were pooled and DNA from the control subjects were pooled.  These pooled samples were analysed using the HumanMethylation 450K BeadChip array.

Results: Comparison of the methylation profiles between obese and control subjects revealed 80 differentially methylated CpG (DMCpG) loci associated with 80 unique genes that had a greater than 10% difference in methylation and a p value<0.05. The top pathways enriched amongst the DMCpGs were cellular developmental, growth and proliferation and cell to cell signaling. To validate the associations between the methylation of selected DMCpGs with childhood obesity, pyrosequencing-based bisulfite PCR analysis was carried out across the DMCpGs within FYN, IGFBP3, PIWIL4 and TAOK3 in individual subjects.  
FYN (Cg26846943) was hypermethylated in obese individuals (p=0.012), while lower methylation of IGFBP3 (Cg17209188, p=0.001), PIWIL4 (Cg16436, p=0.003) and TAOK3 (Cg17627898, p=0.001) were associated with obesity.

Conclusions: In conclusion, our genome wide analysis provides evidence that childhood obesity is associated with changes in DNA methylation in whole blood. These findings suggest that epigenetic processes and early life programming may play a role in the pathogenesis of childhood obesity.  Further studies are required to determine the causal direction of this relationship.