Epigenome-wide association study of long-term psychosocial stress in older adults.

TitleEpigenome-wide association study of long-term psychosocial stress in older adults.
Publication TypeJournal Article
Year of Publication2024
AuthorsOpsasnick, LA, Zhao, W, Schmitz, LL, Ratliff, SM, Faul, JD, Zhou, X, Needham, BL, Smith, JA
ISSN Number1559-2308
KeywordsDNA Methylation, Epigenome, Smoking, Stress, Psychological, Tobacco Smoking

Long-term psychosocial stress is strongly associated with negative physical and mental health outcomes, as well as adverse health behaviours; however, little is known about the role that stress plays on the epigenome. One proposed mechanism by which stress affects DNA methylation is through health behaviours. We conducted an epigenome-wide association study (EWAS) of cumulative psychosocial stress ( = 2,689) from the Health and Retirement Study (mean age = 70.4 years), assessing DNA methylation (Illumina Infinium HumanMethylationEPIC Beadchip) at 789,656 CpG sites. For identified CpG sites, we conducted a formal mediation analysis to examine whether smoking, alcohol use, physical activity, and body mass index (BMI) mediate the relationship between stress and DNA methylation. Nine CpG sites were associated with psychosocial stress (all  < 9E-07; FDR q < 0.10). Additionally, health behaviours and/or BMI mediated 9.4% to 21.8% of the relationship between stress and methylation at eight of the nine CpGs. Several of the identified CpGs were in or near genes associated with cardiometabolic traits, psychosocial disorders, inflammation, and smoking. These findings support our hypothesis that psychosocial stress is associated with DNA methylation across the epigenome. Furthermore, specific health behaviours mediate only a modest percentage of this relationship, providing evidence that other mechanisms may link stress and DNA methylation.

Citation Key13801
PubMed ID38431869
PubMed Central IDPMC10913704
Grant ListR00 AG056599 / AG / NIA NIH HHS / United States
R01 HL141292 / HL / NHLBI NIH HHS / United States
T32 HG000040 / HG / NHGRI NIH HHS / United States
U01 AG009740 / AG / NIA NIH HHS / United States