Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference

ObjectiveTo conduct an epigenome-wide analysis of DNA methylation and obesity traits. MethodsDNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family structure, was modeled. ResultsEpigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n=2,377) and the Atherosclerosis Risk in Communities study (n=2,097), were found. Top findings were in CPT1A (meta-analysis P=2.7 x 10(-43) for BMI and 9.9 x 10(-23) for WC), PHGDH (meta-analysis P=2.0 x 10(-15) for BMI and 4.0 x 10(-9) for WC), CD38 (meta-analysis P=6.3 x 10(-11) for BMI and 1.6 x 10(-12) for WC), and long intergenic non-coding RNA 00263 (meta-analysis P=2.2 x 10(-16) for BMI and 8.9 x 10(-14) for WC), regions with biologically plausible relationships to adiposity. ConclusionsThis large-scale epigenome-wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications.