Associations of LEP, CRH, ICAM-1, and LINE-1 methylation, measured in saliva, with waist circumference, body mass index, and percent body fat in mid-childhood

Background: Genetics explains a small proportion of variance in body mass index at the population level. Epigenetics, commonly measured by gene methylation, holds promise for understanding obesity risk factors and mechanisms. Methods: Participants were 431 adolescents aged 10–15 years. BMI z-score, waist circumference z-score, and percent body fat were measured. Saliva samples were collected and methylation of promoter regions of four candidate genes or sequences (LEP, ICAM-1, CRH, and LINE-1) were measured in 3–4 CpG sites each. Linear regression was used to identify associations of methylation with obesity-related outcomes. Results: After adjusting for age, in sex-stratified analysis, the three obesity-related outcomes were negatively associated with LEP methylation in obese boys only. There were no associations of methylation of the other genes or sequences and the obesity-related outcomes. Conclusions: Our results are consistent with prior studies that reported sex differences in associations of obesity-related outcomes with LEP methylation, and also as would be expected in adipose tissue, the source of circulating leptin. The findings suggest that saliva might be an acceptable tissue for epigenetics studies in adolescents.