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

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 (n = 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 p < 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.</p

Additional file 1 of Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance

Additional file 1: Supplemental Text. Table S1. Sample size and the number of SNPs in the paragraph delayed recall GWAS from each discovery and replication cohort. Table S2. Sample size and the number of SNPs in the word list delayed recall GWAS from each discovery and replication cohort. Table S3. Tissue-specific relationships between delayed recall test (PAR-dr and WL-dr) summary SNP associations and eQTLs and meQTLs. Table S4. Relationship Between Delayed Recall Summary Gene Associations and Transcription Factor Genes. Table S5. Significant Genes Associated with Paragraph Delayed Recall (PAR-dr) and Word List Delayed Recall (WL-dr). Table S6. Significant component genes in the six memory-associated pathways. Table S7. Homologous genes in memory-associated pathways for differential expression analysis. Figure S1. GWAS cohorts and microarray expression datasets. Figure S2. Design of the pathway analyses. Figure S3. Forest plots of significant pathway enrichment effects and p-values from discovery cohorts (Approach 1)