Childhood adversity predicts black young adults’ DNA methylation-based accelerated aging: A dual pathway model

2021 ◽  
pp. 1-15
Author(s):  
Steven R. H. Beach ◽  
Frederick X. Gibbons ◽  
Sierra E. Carter ◽  
Mei Ling Ong ◽  
Justin A. Lavner ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Accelerated Aging ◽  
Childhood Adversity ◽  
Health Study ◽  
Early Exposure ◽  
Contrast Effects ◽  
Pathway Model ◽  
Dual Pathway ◽  
Study Participants ◽  
Biological Outcomes

Abstract We expand upon prior work (Gibbons et al., 2012) relating childhood stressor effects, particularly harsh childhood environments, to risky behavior and ultimately physical health by adding longer-term outcomes – deoxyribonucleic acid (DNA) methylation-based measures of accelerated aging (DNAm-aging). Further, following work on the effects of early exposure to danger (McLaughlin et al., 2014), we also identify an additional pathway from harsh childhood environments to DNAm-aging that we label the danger/FKBP5 pathway, which includes early exposure to dangerous community conditions that are thought to impact glucocorticoid regulation and pro-inflammatory mechanisms. Because different DNAm-aging indices provide different windows on accelerated aging, we contrast effects on early indices of DNAm-aging based on chronological age with later indices that focused on predicting biological outcomes. We utilize data from Family and Community Health Study participants (N = 449) from age 10 to 29. We find that harshness influences parenting, which, in turn, influences accelerated DNAm-aging through the risky cognitions and substance use (i.e., behavioral) pathway outlined by Gibbons et al. (2012). Harshness is also associated with increased exposure to threat/danger, which, in turn, leads to accelerated DNAm-aging through effects on FKBP5 activity and enhanced pro-inflammatory tendencies (i.e., the danger/FKBP5 pathway).

scholarly journals MCR: Open-Source Software to Automate Compilation of Health Study Report-Back

2021 ◽  
Vol 18 (11) ◽  
pp. 6104
Author(s):  
Erin Polka ◽  
Ellen Childs ◽  
Alexa Friedman ◽  
Kathryn S. Tomsho ◽  
Birgit Claus Henn ◽  
...  
Keyword(s):  
Quality Control ◽  
Open Source ◽  
Open Source Software ◽  
Research Team ◽  
Self Determination ◽  
Health Study ◽  
Equitable Access ◽  
Team Members ◽  
Study Participants ◽  
The Impact

Sharing individualized results with health study participants, a practice we and others refer to as “report-back,” ensures participant access to exposure and health information and may promote health equity. However, the practice of report-back and the content shared is often limited by the time-intensive process of personalizing reports. Software tools that automate creation of individualized reports have been built for specific studies, but are largely not open-source or broadly modifiable. We created an open-source and generalizable tool, called the Macro for the Compilation of Report-backs (MCR), to automate compilation of health study reports. We piloted MCR in two environmental exposure studies in Massachusetts, USA, and interviewed research team members (n = 7) about the impact of MCR on the report-back process. Researchers using MCR created more detailed reports than during manual report-back, including more individualized numerical, text, and graphical results. Using MCR, researchers saved time producing draft and final reports. Researchers also reported feeling more creative in the design process and more confident in report-back quality control. While MCR does not expedite the entire report-back process, we hope that this open-source tool reduces the barriers to personalizing health study reports, promotes more equitable access to individualized data, and advances self-determination among participants.

scholarly journals Combined effects of genotype and childhood adversity shape variability of DNA methylation across age

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Darina Czamara ◽  
Elleke Tissink ◽  
Johanna Tuhkanen ◽  
Jade Martins ◽  
Yvonne Awaloff ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Social Services ◽  
Disease Risk ◽  
Childhood Adversity ◽  
Total Sample ◽  
Synaptic Function ◽  
Combined Effects ◽  
Self Reports ◽  
Main Effects ◽  
The Impact

AbstractLasting effects of adversity, such as exposure to childhood adversity (CA) on disease risk, may be embedded via epigenetic mechanisms but findings from human studies investigating the main effects of such exposure on epigenetic measures, including DNA methylation (DNAm), are inconsistent. Studies in perinatal tissues indicate that variability of DNAm at birth is best explained by the joint effects of genotype and prenatal environment. Here, we extend these analyses to postnatal stressors. We investigated the contribution of CA, cis genotype (G), and their additive (G + CA) and interactive (G × CA) effects to DNAm variability in blood or saliva from five independent cohorts with a total sample size of 1074 ranging in age from childhood to late adulthood. Of these, 541 were exposed to CA, which was assessed retrospectively using self-reports or verified through social services and registries. For the majority of sites (over 50%) in the adult cohorts, variability in DNAm was best explained by G + CA or G × CA but almost never by CA alone. Across ages and tissues, 1672 DNAm sites showed consistency of the best model in all five cohorts, with G × CA interactions explaining most variance. The consistent G × CA sites mapped to genes enriched in brain-specific transcripts and Gene Ontology terms related to development and synaptic function. Interaction of CA with genotypes showed the strongest contribution to DNAm variability, with stable effects across cohorts in functionally relevant genes. This underscores the importance of including genotype in studies investigating the impact of environmental factors on epigenetic marks.

scholarly journals Accelerated aging in normal breast tissue of women with breast cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Shoghag Panjarian ◽  
Jozef Madzo ◽  
Kelsey Keith ◽  
Carolyn M. Slater ◽  
Carmen Sapienza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Anomaly Detection ◽  
Breast Tissue ◽  
Preventive Intervention ◽  
Normal Breast Tissue ◽  
Accelerated Aging ◽  
Normal Breast ◽  
Age Related ◽  
Unsupervised Anomaly Detection

Abstract Background DNA methylation alterations have similar patterns in normal aging tissue and in cancer. In this study, we investigated breast tissue-specific age-related DNA methylation alterations and used those methylation sites to identify individuals with outlier phenotypes. Outlier phenotype is identified by unsupervised anomaly detection algorithms and is defined by individuals who have normal tissue age-dependent DNA methylation levels that vary dramatically from the population mean. Methods We generated whole-genome DNA methylation profiles (GSE160233) on purified epithelial cells and used publicly available Infinium HumanMethylation 450K array datasets (TCGA, GSE88883, GSE69914, GSE101961, and GSE74214) for discovery and validation. Results We found that hypermethylation in normal breast tissue is the best predictor of hypermethylation in cancer. Using unsupervised anomaly detection approaches, we found that about 10% of the individuals (39/427) were outliers for DNA methylation from 6 DNA methylation datasets. We also found that there were significantly more outlier samples in normal-adjacent to cancer (24/139, 17.3%) than in normal samples (15/228, 5.2%). Additionally, we found significant differences between the predicted ages based on DNA methylation and the chronological ages among outliers and not-outliers. Additionally, we found that accelerated outliers (older predicted age) were more frequent in normal-adjacent to cancer (14/17, 82%) compared to normal samples from individuals without cancer (3/17, 18%). Furthermore, in matched samples, we found that the epigenome of the outliers in the pre-malignant tissue was as severely altered as in cancer. Conclusions A subset of patients with breast cancer has severely altered epigenomes which are characterized by accelerated aging in their normal-appearing tissue. In the future, these DNA methylation sites should be studied further such as in cell-free DNA to determine their potential use as biomarkers for early detection of malignant transformation and preventive intervention in breast cancer.

scholarly journals Is behaving unethically for organizations a mixed blessing? A dual-pathway model for the work-to-family spillover effects of unethical pro-organizational behavior

2021 ◽  
Author(s):  
Haixiao Chen ◽  
Ho Kwong Kwan ◽  
Jie Xin
Keyword(s):  
Organizational Behavior ◽  
Family Conflict ◽  
Spillover Effects ◽  
Self Esteem ◽  
Conservation Of Resources ◽  
Pathway Model ◽  
Positive Spillover ◽  
Dual Pathway ◽  
Stress At Work ◽  
Mixed Blessing

AbstractThis research examines the mixed work-to-family spillover effects of unethical pro-organizational behavior. Drawing on conservation of resources theory and the work–home resources model, we develop a dual-pathway model to explain such effects. Based on a three-wave field study involving 214 respondents in China, we find engagement in unethical pro-organizational behavior to be positively associated with employees’ organization-based self-esteem and stress at work, which in turn, leads to work-to-family positive spillover and work-to-family conflict, respectively. We also find that performing tensions moderate the mixed effects of unethical pro-organizational behavior on organization-based self-esteem and work stress and the indirect effects of unethical pro-organizational behavior on work-to-family positive spillover and work-to-family conflict. Our findings have theoretical implications for business ethics scholars and practical implications for managers.

scholarly journals Rationalizing Thyroid Function Testing: Which TSH Cutoffs Are Optimal for Testing Free T4?

2017 ◽  
Vol 102 (11) ◽  
pp. 4235-4241 ◽  
Author(s):  
Meg Henze ◽  
Suzanne J Brown ◽  
Narelle C Hadlow ◽  
John P Walsh
Keyword(s):  
Thyroid Function ◽  
Reference Range ◽  
Health Study ◽  
Free T4 ◽  
Clinical Cohort ◽  
Thyroid Function Testing ◽  
Reflex Testing ◽  
Study Participants ◽  
Function Testing ◽  
Tsh Levels

Abstract Context Thyroid function testing often uses thyrotropin (TSH) measurement first, followed by reflex testing for free thyroxine (T4) if TSH is outside the reference range. The utility of different TSH cutoffs for reflex testing is unknown. Objective To examine different TSH cutoffs for reflex free T4 testing. Design, Setting, and Patients We analyzed concurrent TSH and free T4 results from 120,403 individuals from a single laboratory in Western Australia (clinical cohort) and 4568 Busselton Health Study participants (community cohort). Results In the clinical cohort, restricting free T4 measurement to individuals with TSH <0.3 or >5.0 mU/L resulted in a 22% reduction in free T4 testing compared with a TSH reference range of 0.4 to 4.0 mU/L; using TSH cutoffs of 0.2 and 6.0 mU/L resulted in a 34% reduction in free T4 testing. In the community cohort, the corresponding effect was less: 3.3% and 4.8% reduction in free T4 testing. In the clinical cohort, using TSH cutoffs of 0.2 and 6.0 mU/L, elevated free T4 would go undetected in 4.2% of individuals with TSH levels of 0.2 to 0.4 mU/L. In most, free T4 was marginally elevated and unlikely to indicate clinically relevant hyperthyroidism. Low free T4 would go undetected in 2.5% of individuals with TSH levels of 4 to 6 mU/L; in 94%, free T4 was marginally reduced and unlikely to indicate clinically relevant hypothyroidism. Conclusions Setting TSH cutoffs at 0.1 to 0.2 mU/L less than and 1 to 2 mU/L greater than the reference range for reflex testing of free T4 would reduce the need for free T4 testing, with minimal effect on case finding.

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