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.
Department of Psychiatry, Yale School of Medicine, 300 George street, Suite 901, New Haven, CT 06511, United States; Connecticut Veteran Health System, 950 Campbell Ave, Building 35, Room #43, West Haven, 06516, United States. Electronic address: ke.xu@yale.edu.
Ke
K
Xu
Department of Psychiatry, Yale School of Medicine, 300 George street, Suite 901, New Haven, CT 06511, United States; Connecticut Veteran Health System, 950 Campbell Ave, Building 35, Room #43, West Haven, 06516, United States.
Xinyu
X
Zhang
Department of Biostatistics, Yale School of Public Health, New Haven, CT 06511, United States.
Zuoheng
Z
Wang
Yale Stress Center, Yale University, 2 Church St S #209, New Haven, CT 06519, United States.
Ying
Y
Hu
Department of Psychiatry, Yale School of Medicine, 300 George street, Suite 901, New Haven, CT 06511, United States; Center for Biomedical Informatics and Information Technology, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850, United States.
Rajita
R
Sinha
D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D057890:Epigenomics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000523:psychology; D013315:Stress, Psychological / Q000235:genetics*; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics*; D055815:Young Adult
C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein
Body mass index; Cumulative stress; Epigenome-wide association; Obesity; SOCS3