女性和男性中 DNA 甲基化与乐观的全基因组关联分析。

Epigenome-Wide Analysis of DNA Methylation and Optimism in Women and Men.

机构信息

From the Department of Environmental Health (Wang, Fong, Schwartz), Harvard T.H. Chan School of Public Health; Department of Medicine, Brigham and Women's Hospital (DeMeo, Manson), Harvard Medical School; Channing Division of Network Medicine (DeMeo, Grodstein), Brigham and Women's Hospital; Department of Social and Behavioral Sciences (Kim, Kubzansky) and Lee Kum Sheung Center for Health and Happiness (Kim, Kubzansky), Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Psychology (Kim), University of British Columbia, Vancouver, BC, Canada; Division of Environmental Health Sciences (Cardenas), School of Public Health, University of California, Berkeley, Berkeley, California; Department of Population Medicine, Division of Chronic Disease Research Across the Lifecourse (Cardenas), Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts; School of the Environment (Fong), Yale University, New Haven, Connecticut; National Center for Posttraumatic Stress Disorder (Lee), VA Boston Healthcare System; Department Psychiatry (Lee, Spiro), Boston University School of Medicine; Massachusetts Veterans Epidemiology Research and Information Center (Spiro), Veterans Affairs Boston Healthcare System; Department of Epidemiology (Spiro), Boston University School of Public Health, Boston, Massachusetts; Department of Epidemiology (Whitsel), Gillings School of Global Public Health; Department of Medicine (Whitsel), School of Medicine, University of North Carolina, Chapel Hill, North Carolina; Departments of Human Genetics (Horvath) and Biostatistics (Horvath), David Geffen School of Medicine, University of California, Los Angeles, California; Department of Preventive Medicine (Hou), Northwestern Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Department of Environmental Health Sciences (Baccarelli), Columbia Mailman School of Public Health, New York, New York; Departments of Genetics (Li), Biostatistics (Li), and Computer Science (Li), University of North Carolina; Cardiovascular Program, Department of Epidemiology (Stewart), University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina; and Department of Epidemiology (Manson, Grodstein, Schwartz), Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

出版信息

Psychosom Med. 2023 Jan 1;85(1):89-97. doi: 10.1097/PSY.0000000000001147. Epub 2022 Oct 3.

DOI:10.1097/PSY.0000000000001147

PMID:36201768

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9771983/

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.

摘要

目的

更高的乐观程度与降低死亡率和降低与年龄相关的慢性疾病风险相关。DNA 甲基化（DNAm）可能为这些关系的潜在机制提供深入了解。我们假设，在乐观程度较高和较低的老年人中，DNAm 会有所不同。

方法

使用来自两个具有不同种族/族裔（n=3816）的女性和男性（仅为白人，n=667）的基于人群的队列的横断面数据，我们研究了乐观程度与全白细胞 DNAm 的关联。随后使用随机效应荟萃分析来汇总个体结果。通过“独立自由度数量”方法鉴定出差异甲基化的胞嘧啶-磷酸-鸟嘌呤（CpG）：使用主成分（PC）数量进行有效自由度校正，解释 DNAm 数据的>95％的变化（PC 校正）。我们使用 comb-p 进行区域分析，并使用Ingenuity Pathway Analysis 软件进行途径分析。

结果

我们发现，在 DNAm-乐观关联中，基本上所有 CpG（总探针 N=359862）在性别和种族/族裔方面都是同质的。在基于同质 CpG 的单个 CpG 位点分析中，我们使用 PC 校正鉴定出了 13 个差异甲基化探针。我们发现了四个差异甲基化区域和两个差异甲基化途径。单个 CpG 位点和区域分析的注释基因涉及精神疾病，心血管疾病，认知障碍和癌症。鉴定出的途径与癌症以及神经发育和神经退行性疾病有关。