Epigenome-wide association study in childhood obesity

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.

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). 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, which allows determining whether a particular CpG site is causal or consequence for the disease. Strikingly, we found that 2 of the 5 CpG sites mapping the SPATC1L locus are causal for multiple disorders, including not only childhood obesity, but also 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 (Collagen Type VI Alpha 2 Chain), LSS (Lanosterol Synthase), YBEY (YbeY Metallopeptidase) and C21orf58 were differentially expressed between the two groups.

Together, we show that 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.