Evidence map›Paper›PMID 36379232›Full record

ArticleEnvironmental research2023

Epigenome-wide DNA methylation in leukocytes and toenail metals: The normative aging study.

Cuicui Wang, Zongli Xu, Xinye Qiu, Yaguang Wei, Adjani A Peralta, Mahdieh Danesh Yazdi, Tingfan Jin, Wenyuan Li, Allan Just, Jonathan Heiss and 9 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Environmental research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.6field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 7 institutions in 2 countries.

Cuicui WangDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: cuicuiwang@hsph.harvard.edu.
Zongli XuEpidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
Xinye QiuDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Yaguang WeiDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Adjani A PeraltaDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Mahdieh Danesh YazdiDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Program in Public Health, Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA.
Tingfan JinDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Wenyuan LiSchool of Public Health and Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Allan JustDepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Jonathan HeissDepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Lifang HouDepartment of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Yinan ZhengDepartment of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Brent A CoullDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
Anna KoshelevaDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
David SparrowVA Normative Aging Study, VA Boston Healthcare System, Boston, MA 02130, USA; Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Chitra AmarasiriwardenaDepartment of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Robert O WrightDepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Andrea A BaccarelliDepartment of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY 10032, USA.
Joel D SchwartzDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Harvard University · USIcahn School of Medicine at Mount Sinai · USNorthwestern University · USBoston University · USColumbia University · USNational Institute of Environmental Health Sciences · USSecond Affiliated Hospital of Zhejiang University · CN

Funding

True Metal fac coreP30ES009089 · NIEHS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Steven N. Chillrud · 1998 to 2026
$44.7M
Translational Research Support CoreP30ES000002 · NIEHS · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI JAIME ELIZABETH HART · 1985 to 2026
$44.6M
Air Particulate, Metals, and Cognitive Performance in an Aging Cohort- Roles of Circulating Extracellular Vesicles and Non-coding RNAsR01ES027747 · NIEHS · HARVARD SCHOOL OF PUBLIC HEALTH · PI SCHWARTZ, JOEL D · 2017 to 2021
$3.7M
Circulating microRNAs in Extracellular Vesicles, Air Particulate Pollution, and Lung Function in an Aging CohortR01ES025225 · NIEHS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BACCARELLI, ANDREA · 2016 to 2020
$2.9M
NIEHS NIH HHS P30 ES000002NIEHS NIH HHS P30 ES009089NIEHS NIH HHS R01 ES025225NIEHS NIH HHS R01 ES027747
6 · The paper itself

Abstract

backgroundEnvironmental metal exposures have been associated with multiple deleterious health endpoints. DNA methylation (DNAm) may provide insight into the mechanisms underlying these relationships. Toenail metals are non-invasive biomarkers, reflecting a medium-term time exposure window.

objectivesThis study examined variation in leukocyte DNAm and toenail arsenic (As), cadmium (Cd), lead (Pb), manganese (Mn), and mercury (Hg) among elderly men in the Normative Aging Study, a longitudinal cohort.

methodsWe repeatedly collected samples of blood and toenail clippings. We measured DNAm in leukocytes with the Illumina HumanMethylation450 K BeadChip. We first performed median regression to evaluate the effects of each individual toenail metal on DNAm at three levels: individual cytosine-phosphate-guanine (CpG) sites, regions, and pathways. Then, we applied a Bayesian kernel machine regression (BKMR) to assess the joint and individual effects of metal mixtures on DNAm. Significant CpGs were identified using a multiple testing correction based on the independent degrees of freedom approach for correlated outcomes. The approach considers the effective degrees of freedom in the DNAm data using the principal components that explain >95% variation of the data.

resultsWe included 564 subjects (754 visits) between 1999 and 2013. The numbers of significantly differentially methylated CpG sites, regions, and pathways varied by metals. For example, we found six significant pathways for As, three for Cd, and one for Mn. The As-associated pathways were associated with cancer (e.g., skin cancer) and cardiovascular disease, whereas the Cd-associated pathways were related to lung cancer. Metal mixtures were also associated with 47 significant CpG sites, as well as pathways, mainly related to cancer and cardiovascular disease.

conclusionsThis study provides an approach to understanding the potential epigenetic mechanisms underlying observed relations between toenail metals and adverse health endpoints.

Indexed as

ArsenicCardiovascular DiseasesMercuryAgedAgingBayes TheoremCadmiumDNA MethylationEpigenomeHumansLeukocytesMaleManganeseMetalsNailsArsenicCadmiumManganeseMercuryMetalsDNA MethylationEpigenome-wide association studyJoint effectsPathway analysisToenail metals

Identifiers

PMID36379232
PMCPMC9825663
OpenAlexW4309077687

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.