Epigenome-Wide Analysis of DNA Methylation and Optimism in Women and Men. Issue 1 (3rd January 2023)

• Record Type: Journal Article
• Authors: Wang, Cuicui; DeMeo, Dawn L.; Kim, Eric S.; Cardenas, Andres; Fong, Kelvin C.; Lee, Lewina O.; Spiro, Avron; Whitsel, Eric A.; Horvath, Steve; Hou, Lifang; Baccarelli, Andrea A.; Li, Yun; Stewart, James D.; Manson, JoAnn E.; Grodstein, Francine; Kubzansky, Laura D.; Schwartz, Joel D.
• Is Part Of: Psychosomatic medicine. Volume 85:Issue 1(2023)
• Page Start: 89
• Page End: 97
• Publication Date: 2023-01-03
• Subjects: optimism -- DNA methylation -- epigenome-wide association study -- mechanism -- AA = African American -- CHD = coronary heart disease -- CpGs = cytosine-phosphate-guanines -- DMPs = differentially methylated probes -- DMRs = differently methylated regions -- DNAm = DNA methylation -- EWAS = epigenome-wide association study -- NAS = Normative Aging Study -- NIDF = number of independent degrees of freedom -- PCs = principal components -- PSM-R = Revised Optimism-Pessimism Scale -- SCZ = schizophrenia -- SD = standard deviation -- WHI = Women's Health Initiative; Medicine, Psychosomatic -- Periodicals; 616.0805
• DOI: 10.1097/PSY.0000000000001147
• Languages: English
• ISSNs: 0033-3174

Abstract

ABSTRACT: Objective: Higher optimism is associated with reduced mortality and a lower risk of age-related chronic diseases. DNA methylation (DNAm) may provide insight into mechanisms underlying these relationships. We hypothesized that DNAm would differ among older individuals who are more versus less optimistic. Methods: Using cross-sectional data from two population-based cohorts of women with diverse races/ethnicities ( n = 3816) and men (only White, n = 667), we investigated the associations of optimism with epigenome-wide leukocyte DNAm. Random-effects meta-analyses were subsequently used to pool the individual results. Significantly differentially methylated cytosine-phosphate-guanines (CpGs) were identified by the "number of independent degrees of freedom" approach: effective degrees of freedom correction using the number of principal components (PCs), explaining >95% of the variation of the DNAm data (PC-correction). We performed regional analyses using comb-p and pathway analyses using the Ingenuity Pathway Analysis software. Results: We found that essentially all CpGs (total probe N = 359, 862) were homogeneous across sex and race/ethnicity in the DNAm-optimism association. In the single CpG site analyses based on homogeneous CpGs, we identified 13 significantly differentially methylated probes using PC-correction. We found four significantly differentially methylated regions and two significantly differentially methylated pathways. The annotated genes from the single CpG site and regional analyses are involved in psychiatric disorders, cardiovascular disease, cognitive impairment, and cancer. Identified pathways were related to cancer, and neurodevelopmental and neurodegenerative disorders. Conclusion: Our findings provide new insights into possible mechanisms underlying optimism and health.