Dataset Information

Associations of Heavy Metals with Activities of Daily Living Disability: An Epigenome-Wide View of DNA Methylation and Mediation Analysis.

ABSTRACT:

Background

Exposure to heavy metals has been reported to be associated with multiple diseases. However, direct associations and potential mechanisms of heavy metals with physical disability remain unclear.

Objectives

We aimed to quantify associations of heavy metals with physical disability and further explore the potential mechanisms of DNA methylation on the genome scale.

Methods

A cross-sectional study of 4,391 older adults was conducted and activities of daily living (ADL) disability were identified using a 14-item scale questionnaire including basic and instrumental activities to assess the presence of disability (yes or no) rated on a scale of dependence. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated to quantify associations between heavy metals and ADL disability prevalence using multivariate logistic regression and Bayesian kernel machine regression (BKMR) models. Whole blood-derived DNA methylation was measured using the HumanMethylationEPIC BeadChip array. An ADL disability-related epigenome-wide DNA methylation association study (EWAS) was performed among 212 sex-matched ADL disability cases and controls, and mediation analysis was further applied to explore potential mediators of DNA methylation.

Results

Each 1-standard deviation (SD) higher difference in log10-transformed manganese, copper, arsenic, and cadmium level was significantly associated with a 14% (95% CI: 1.05, 1.24), 16% (95% CI:1.07, 1.26), 22% (95% CI:1.13, 1.33), and 15% (95% CI:1.06, 1.26) higher odds of ADL disability, which remained significant in the multiple-metal and BKMR models. A total of 85 differential DNA methylation sites were identified to be associated with ADL disability prevalence, among which methylation level at cg220000984 and cg23012519 (annotated to IRGM and PKP3) mediated 31.0% and 31.2% of manganese-associated ADL disability prevalence, cg06723863 (annotated to ESRP2) mediated 32.4% of copper-associated ADL disability prevalence, cg24433124 (nearest to IER3) mediated 15.8% of arsenic-associated ADL disability prevalence, and cg07905190 and cg17485717 (annotated to FREM1 and TCP11L1) mediated 21.5% and 30.5% of cadmium-associated ADL disability prevalence (all p<0.05).

Discussion

Our findings suggested that heavy metals contributed to higher prevalence of ADL disability and that locus-specific DNA methylation are partial mediators, providing potential biomarkers for further cellular mechanism studies. https://doi.org/10.1289/EHP10602.

SUBMITTER: Xiao L

PROVIDER: S-EPMC9423034 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Associations of Heavy Metals with Activities of Daily Living Disability: An Epigenome-Wide View of DNA Methylation and Mediation Analysis.

Xiao Lili L Cheng Hong H Cai Haiqing H Wei Yue Y Zan Gaohui G Feng Xiuming X Liu Chaoqun C Li Longman L Huang Lulu L Wang Fei F Chen Xing X Zou Yunfeng Y Yang Xiaobo X

Environmental health perspectives 20220829 8

<h4>Background</h4>Exposure to heavy metals has been reported to be associated with multiple diseases. However, direct associations and potential mechanisms of heavy metals with physical disability remain unclear.<h4>Objectives</h4>We aimed to quantify associations of heavy metals with physical disability and further explore the potential mechanisms of DNA methylation on the genome scale.<h4>Methods</h4>A cross-sectional study of 4,391 older adults was conducted and activities of daily living (A ...[more]

PMID: 36036794

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Project description:BackgroundSocioeconomic status (SES) is associated with both depression and activities of daily living (ADL and IADL). However, the role of ADL as a biological mechanism in the relationship between SES and late-life depression, examined through longitudinal data, remains understudied. This study explored the longitudinal mediation effects of basic ADL or IADL on the SES-depression link in older adults.MethodsData from the China Health and Retirement Longitudinal Study (N = 4104) were utilized. Mediation analysis was performed using parallel process latent growth curve modeling.ResultsThe average age of participants was 57.76 years, and 55.7% being females. Significant linear growth over time was observed in ADL, IADL, and depression. Adjusting for covariates, SES was positively linked to the initial levels (intercepts) of ADL (βiADL=-0.100[-0.143, -0.057]), IADL (βiIADL=-0.140[-0.185, -0.095]), and depression (βiDEP=-0.103[-0.158, -0.048]). However, SES showed no significant correlation with the rate of change (slopes) in ADL, IADL, or depression (P > 0.05). The intercepts of ADL (βiDEP = 0.566[0.503, 0.629]) and IADL (βiDEP = 0.607[0.544, 0.670]) were positively correlated with the depression intercept but negatively with the depression slope. Conversely, the slopes of ADL and IADL were positively associated with the depression slope. These results suggest a negative indirect relationship between SES and the initial level of depression, but a positive indirect relationship with the rate of increase in depression through ADL (or IADL) intercept.ConclusionsHigher SES is associated with a lower initial risk of depression and ADL difficulties. However, this same higher SES may relate to a faster increase in ADL difficulties and depression among middle-aged and older adults. The findings underscore the need for increased governmental healthcare funding and improved healthcare accessibility. Additionally, maintaining adequate sleep and physical activity can help prevent disability and reduce depression risk later in life, particularly among older adults with lower SES.

Project description:BackgroundCardiac arrhythmias are common conditions in older people. Unfortunately, there is limited literature on associations between cardiac arrhythmias and physical performance or disability. We therefore aimed to prospectively investigate associations between cardiac arrhythmias and changes in disability and physical performance during 8 years of follow-up, using data from the Italian Longitudinal Study on Aging (ILSA).MethodsCardiac arrhythmias diagnosis was posed through a screening phase, confirmed by a physician. The onset of disability in activities of daily living (ADL) and the changes in several physical performance tests during follow-up were considered as outcomes. Fully-adjusted and propensity-score Cox Proportional Hazard models and mixed models were used for exploring associations between cardiac arrhythmia and the outcomes of interest.ResultsThe prevalence of cardiac arrhythmia at baseline was 23.3%. People reporting cardiac arrhythmia at the baseline were significantly older, more frequently male, smokers and reported a higher presence of all medical conditions investigated (hypertension, heart failure, angina, myocardial infarction, diabetes, stroke), but no difference in dementia, Parkinsonism, cognitive or mood disorder. Cardiac arrhythmia at baseline was significantly associated with the incidence of disability in ADL (HR = 1.23; 95%: CI: 1.01-1.50; P = 0.0478 in propensity score analyses; HR = 1.28; 95% CI: 1.01-1.61; P = 0.0401 in fully adjusted models). Cardiac arrhythmia at baseline was also associated with a significant worsening in balance test (P = 0.0436).ConclusionsThe presence of cardiac arrhythmia at baseline was associated with a significant higher risk of disability and of worsening in some physical performance tests, particularly those relating to balance. Screening and frequently assessing physical performance in older people affected by cardiac arrhythmia can be important to prevent a loss of physical performance, with further, potential, complications of medical management.

Dataset Information

Associations of Heavy Metals with Activities of Daily Living Disability: An Epigenome-Wide View of DNA Methylation and Mediation Analysis.

Background

Objectives

Methods

Results

Discussion

Publications

Associations of Heavy Metals with Activities of Daily Living Disability: An Epigenome-Wide View of DNA Methylation and Mediation Analysis.

Similar Datasets

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