Epigenome-wide association analysis revealed that SOCS3 methylation influences the effect of cumulative stress on obesity

Chronic stress has a significant impact on obesity. However, how stress influences obesity remains unclear. We conducted an epigenome-wide DNA methylation association analysis of obesity (N=510) and examined whether cumulative stress influenced the DNA methylation on body weight. We identified 20 CpG sites associated with body mass index at the false discovery rate q<0.05, including a novel site, cg18181703, in suppressor of cytokine signaling 3 (SOCS3) gene (coefficient beta=-0.0022, FDR q = 4.94 x 10(-5)). The interaction between cgl 8181703 and cumulative adverse life stress contributed to variations in body weight (p = 0.002). Individuals with at least five major life events and lower methylation of cgl 818703 showed a 1.38-fold higher risk of being obese (95%CI: 1.17-1.76). Our findings suggest that aberrant in DNA methylation is associated with body weight and that methylation of SOCS3 moderates the effect of cumulative stress on obesity. (C) 2016 Elsevier B.V. All rights reserved.