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 β = −0.0022, FDR q = 4.94 × 10−5). The interaction between cg18181703 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 cg1818703 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.