Epigenome-wide association study in Childhood Obesity: Searching for early markers of late disease risk

Rationale: Childhood obesity is one a major Public Health issue. Overweight/obese children have a high risk of being obese as adults and develop other co-morbidities, including type 2 diabetes, cardiovascular disease and several types of cancer. It has been proposed that epigenetic mechanisms might be involved in mediating long-term metabolic dysfunction.

Methods: Here we analyzed DNA methylation profiles (Infinium MethylationEPIC BeadChip, 850K) in whole blood from 26 obese (zBMI > 2) and 12 control lean pre-pubertal children (zBMI < 1).

Results:109 CpG sites appeared differentially methylated between the two groups (methylation change 10% and FDR value <0.05). 5 out of the 109 targets, were located within the SPATC1L (Spermatogenesis and Centriole Associated 1 Like) gene. Next, we performed a Two Sample Mendelian Randomization test, and found that 2 of the 5 CpG sites mapping the SPATC1L locus are causal for multiple disorders, including childhood obesity, type 2 diabetes, ulcerative colitis and inflammatory bowel disease. SPATC1L expression was similar in whole blood of obese and lean subjects. However, the contiguous genes COL6A2 and COL6A3 (Collagen Type VI Alpha 2 and 3 Chains), which are strongly associated to obesity, were differentially expressed between the two groups.

Discussion: Childhood obesity is associated to a small change in DNA methylation (109 CpG sites). In our dataset, only 2 CpG sites appeared to play a causative role in the development of the disease. We hypothesize that these CpG sites might mediate disease risk by modulating the expression of physically close genes.