Evidence map›Paper›PMID 33092652›Full record

ArticleClinical epigenetics2020

Smoking-related changes in DNA methylation and gene expression are associated with cardio-metabolic traits.

Silvana C E Maas, Michelle M J Mens, Brigitte Kühnel, Joyce B J van Meurs, André G Uitterlinden, Annette Peters, Holger Prokisch, Christian Herder, Harald Grallert, Sonja Kunze and 4 more

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

37 citing papers in PubMed, 53 citations in OpenAlex.

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  16. Speeding up interval estimation forbioRxiv : the preprint server for biology · 2024
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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

14 authors at 4 institutions in 2 countries.

Silvana C E MaasDepartment of Epidemiology, Erasmus MC University Medical Center Rotterdam, 3015 GB, Rotterdam, The Netherlands.
Michelle M J MensDepartment of Epidemiology, Erasmus MC University Medical Center Rotterdam, 3015 GB, Rotterdam, The Netherlands.
Brigitte KühnelResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
Joyce B J van MeursDepartment Internal Medicine, Erasmus MC University Medical Center Rotterdam, 3015 GD, Rotterdam, the Netherlands.
André G UitterlindenDepartment of Epidemiology, Erasmus MC University Medical Center Rotterdam, 3015 GB, Rotterdam, The Netherlands.
Annette PetersResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
Holger ProkischInstitute of Neurogenomics, Helmholtz-Zentrum München-German Research Center for Environmental Health, 85764, Neuherberg, Germany.
Christian HerderInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.
Harald GrallertInstitute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
Sonja KunzeResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
Melanie WaldenbergerResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
Maryam KavousiDepartment of Epidemiology, Erasmus MC University Medical Center Rotterdam, 3015 GB, Rotterdam, The Netherlands.
Manfred KayserDepartment of Genetic Identification, Erasmus MC University Medical Center Rotterdam, 3015 GD, Rotterdam, The Netherlands.
Mohsen GhanbariDepartment of Epidemiology, Erasmus MC University Medical Center Rotterdam, 3015 GB, Rotterdam, The Netherlands. m.ghanbari@erasmusmc.nl.ORCID 0000-0002-9476-7143
Erasmus MC · NLHelmholtz Zentrum München · DEDeutsches Diabetes-Zentrum e.V. · DEZimmer Biomet (Netherlands) · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTobacco smoking is a well-known modifiable risk factor for many chronic diseases, including cardiovascular disease (CVD). One of the proposed underlying mechanism linking smoking to disease is via epigenetic modifications, which could affect the expression of disease-associated genes. Here, we conducted a three-way association study to identify the relationship between smoking-related changes in DNA methylation and gene expression and their associations with cardio-metabolic traits.

resultsWe selected 2549 CpG sites and 443 gene expression probes associated with current versus never smokers, from the largest epigenome-wide association study and transcriptome-wide association study to date. We examined three-way associations, including CpG versus gene expression, cardio-metabolic trait versus CpG, and cardio-metabolic trait versus gene expression, in the Rotterdam study. Subsequently, we replicated our findings in The Cooperative Health Research in the Region of Augsburg (KORA) study. After correction for multiple testing, we identified both cis- and trans-expression quantitative trait methylation (eQTM) associations in blood. Specifically, we found 1224 smoking-related CpGs associated with at least one of the 443 gene expression probes, and 200 smoking-related gene expression probes to be associated with at least one of the 2549 CpGs. Out of these, 109 CpGs and 27 genes were associated with at least one cardio-metabolic trait in the Rotterdam Study. We were able to replicate the associations with cardio-metabolic traits of 26 CpGs and 19 genes in the KORA study. Furthermore, we identified a three-way association of triglycerides with two CpGs and two genes (GZMA; CLDND1), and BMI with six CpGs and two genes (PID1; LRRN3). Finally, our results revealed the mediation effect of cg03636183 (F2RL3), cg06096336 (PSMD1), cg13708645 (KDM2B), and cg17287155 (AHRR) within the association between smoking and LRRN3 expression.

conclusionsOur study indicates that smoking-related changes in DNA methylation and gene expression are associated with cardio-metabolic risk factors. These findings may provide additional insights into the molecular mechanisms linking smoking to the development of CVD.

Indexed as

AgedBody Mass IndexCardiometabolic Risk FactorsCardiovascular DiseasesCase-Control StudiesCpG IslandsDNA MethylationEpigenesis, GeneticEpigenomicsFemaleGene ExpressionHumansMaleMiddle AgedNetherlandsPhenotypeTriglyceridesCardio-metabolic traitsDNA methylationEpigeneticsGene expressionSmoking

Identifiers

PMID33092652
PMCPMC7579899
OpenAlexW3094437474

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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 OpenQuestion graph.