Evidence map›Paper›PMID 39138531›Full record

ArticleClinical epigenetics2024

Epigenome-wide association study on the plasma metabolome suggests self-regulation of the glycine and serine pathway through DNA methylation.

Jiafei Wu, Victoria Palasantzas, Sergio Andreu-Sánchez, Torsten Plösch, Sam Leonard, Shuang Li, Marc Jan Bonder, Harm-Jan Westra, Joyce van Meurs, Mohsen Ghanbari and 5 more

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Article in Clinical epigenetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

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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

5 citing papers in PubMed.

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4 · The record

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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

15 authors.

Jiafei WuDepartment of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Victoria PalasantzasDepartment of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Sergio Andreu-SánchezDepartment of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Torsten PlöschDepartment of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Sam LeonardDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Shuang LiDepartment of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Marc Jan BonderDepartment of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Harm-Jan WestraDepartment of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Joyce van MeursDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Mohsen GhanbariDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Lude FrankeDepartment of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Alexandra ZhernakovaDepartment of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Jingyuan FuDepartment of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Joanne A HoogerlandDepartment of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands. j.a.hoogerland@umcg.nl.
Daria V ZhernakovaDepartment of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands. d.pital-zhernakova@umcg.nl.

Funding

Dutch Heart Foundation IN-CONTROL (CVON2018-27)European Research Council Consolidator grant 101001678European Research Council Starting Grant 715772Netherlands Organization for Scientific Research (NWO) VENI grant 194.006Netherlands Organization for Scientific Research (NWO) VICI grant VI.C.202.022Netherlands Organization for Scientific Research (NWO) VIDI grant 016.178.056Netherlands Organization for Scientific Research (NWO) ZonMW-VICI 09150182010019Netherlands Organ-on-Chip Initiative NWO Gravitation project (024.003.001)
6 · The paper itself

Abstract

backgroundThe plasma metabolome reflects the physiological state of various biological processes and can serve as a proxy for disease risk. Plasma metabolite variation, influenced by genetic and epigenetic mechanisms, can also affect the cellular microenvironment and blood cell epigenetics. The interplay between the plasma metabolome and the blood cell epigenome remains elusive. In this study, we performed an epigenome-wide association study (EWAS) of 1183 plasma metabolites in 693 participants from the LifeLines-DEEP cohort and investigated the causal relationships in DNA methylation-metabolite associations using bidirectional Mendelian randomization and mediation analysis.

resultsAfter rigorously adjusting for potential confounders, including genetics, we identified five robust associations between two plasma metabolites (L-serine and glycine) and three CpG sites located in two independent genomic regions (cg14476101 and cg16246545 in PHGDH and cg02711608 in SLC1A5) at a false discovery rate of less than 0.05. Further analysis revealed a complex bidirectional relationship between plasma glycine/serine levels and DNA methylation. Moreover, we observed a strong mediating role of DNA methylation in the effect of glycine/serine on the expression of their metabolism/transport genes, with the proportion of the mediated effect ranging from 11.8 to 54.3%. This result was also replicated in an independent population-based cohort, the Rotterdam Study. To validate our findings, we conducted in vitro cell studies which confirmed the mediating role of DNA methylation in the regulation of PHGDH gene expression.

conclusionsOur findings reveal a potential feedback mechanism in which glycine and serine regulate gene expression through DNA methylation.

Indexed as

DNA MethylationEpigenesis, GeneticGenome-Wide Association StudyGlycineMetabolomeSerineAdultAgedCpG IslandsEpigenomeFemaleHumansMaleMendelian Randomization AnalysisMiddle AgedGlycineSerineCardiometabolic diseasesDNA methylationEpigenome-wide association study (EWAS)Gene regulationMetabolomics

Identifiers

PMID39138531
PMCPMC11323446

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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.