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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 89-97 |
| Number of pages | 9 |
| Journal | Psychosomatic medicine |
| Volume | 85 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2023 |
Funding
The authors acknowledge all participants in these studies. They also thank Dr. Zongli Xu from the National Institute of Environmental Health Sciences for conducting pathway analyses using the Ingenuity Pathway Analysis database. Epigenetic Mechanisms of PM-Mediated Cardiovascular Disease (WHI_AS315) was supported by National Institutes of Health (NIH)/National Institute of Environmental Health Sciences grant R01-ES020836. Integrative Genomics and Risk of Coronary Heart Disease and Related Phenotypes (WHI_BAA23) was supported by the National Heart, Lung, and Blood Institute; the NIH; the US Department of Health and Human Services (HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C); and the National Institute of Aging (1U01AG060908-01). Investigator effort for this study was supported by a grant from the National Institute of Aging (R01-AG53273). The Normative Aging Study is a research component of the Massachusetts Veterans Epidemiology Research and Information Center and is supported by the Veterans Affairs Cooperative Studies Program/Epidemiological Research Centers. The Normative Aging Study is also supported by grants from the National Institute of Aging (R01-AG018436, K99-AG055696, K08-AG048221) and National Institute of Environmental Health Sciences (R01-ES015172, 1R01-ES027747, R01-ES031259, R01-ES021733), and a Senior Research Career Scientist award from the Veterans Affairs Clinical Science R&D Service. The views expressed in this article are those of the authors and do not necessarily represent the views of funding bodies such as the National Heart, Lung, and Blood Institute; the NIH; or the US Departments of Health and Human Services and Veterans Affairs. The authors acknowledge all participants in these studies. They also thank Dr. Zongli Xu from the National Institute of Environmental Health Sciences for conducting pathway analyses using the Ingenuity Pathway Analysis database. Epigenetic Mechanisms of PM-Mediated Cardiovascular Disease (WHI_AS315) was supported by National Institutes of Health (NIH)/National Institute of Environmental Health Sciences grant R01-ES020836. Integrative Genomics and Risk of Coronary Heart Disease and Related Phenotypes (WHI_BAA23) was supported by the National Heart, Lung, and Blood Institute; the NIH; the US Department of Health and Human Services (HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C); and the National Institute of Aging (1U01AG060908-01). Investigator effort for this study was supported by a grant from the National Institute of Aging (R01-AG53273). The Normative Aging Study is a research component of the Massachusetts Veterans Epidemiology Research and Information Center and is supported by the Veterans Affairs Cooperative Studies Program/Epidemiological Research Centers. The Normative Aging Study is also supported by grants from the National Institute of Aging (R01-AG018436, K99-AG055696, K08-AG048221) and National Institute of Environmental Health Sciences (R01-ES015172, 1R01-ES027747, R01-ES031259, R01-ES021733), and a Senior Research Career Scientist award from the Veterans Affairs Clinical Science R&D Service. The views expressed in this article are those of the authors and do not necessarily represent the views of funding bodies such as the National Heart, Lung, and Blood Institute; the NIH; or the US Departments of Health and Human Services and Veterans Affairs. Source of Funding and Conflicts of Interest: Dr. DeMeo has received grant support from Bayer and honoraria from Novartis. The other authors report no financial relationships with commercial interests. Source of Funding and Conflicts of Interest: Dr. DeMeo has received grant support from Bayer and honoraria from Novartis. The other authors report no financial relationships with commercial interests.
Keywords
- DNA methylation
- epigenome-wide association study
- mechanism
- optimism
ASJC Scopus subject areas
- Applied Psychology
- Psychiatry and Mental health
