Evidence map›Paper›PMID 42021410›Full record

ArticleClinical epigenetics2026

The non-linear and linear effects of CYP2C19 metaboliser status on DNA methylation: a methylome-wide association study.

Chen Shen, Mark J Adams, Eleanor Davyson, Matthew H Iveson, Simon R Cox, Sarah E Harris, Andrew M McIntosh, Xueyi Shen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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

1 citing paper in PubMed.

  1. Article
4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Chen ShenMRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
Mark J AdamsInstitute for Neuroscience and Cardiovascular Research, The University of Edinburgh, GU305, Chancellor's Building, Royal Infirmary, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
Eleanor DavysonInstitute for Neuroscience and Cardiovascular Research, The University of Edinburgh, GU305, Chancellor's Building, Royal Infirmary, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
Matthew H IvesonInstitute for Neuroscience and Cardiovascular Research, The University of Edinburgh, GU305, Chancellor's Building, Royal Infirmary, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
Simon R CoxLothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, UK.
Sarah E HarrisLothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, UK.
Andrew M McIntoshInstitute for Neuroscience and Cardiovascular Research, The University of Edinburgh, GU305, Chancellor's Building, Royal Infirmary, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
Xueyi ShenInstitute for Neuroscience and Cardiovascular Research, The University of Edinburgh, GU305, Chancellor's Building, Royal Infirmary, 49 Little France Crescent, Edinburgh, EH16 4SB, UK. xueyi.shen@ed.ac.uk.

Funding

Biotechnology and Biological Sciences Research Council BB/W008793/1Chief Scientist Office, Scottish Government Health and Social Care Directorate CZD/16/6Medical Research Council G0701120, G1001245, MR/M013111/1, MR/R024065/1Medical Research Council MR/W014386/1National Alliance for Research on Schizophrenia and Depression 27404NIH HHS R01AG054628; U01AG083829NIHR Imperial Biomedical Research Centre PSR917Scottish Funding Council HR03006UK Research and Innovation EP/S02431X/1Wellcome Trust 220857/Z/20/Z, 104036/Z/14/Z and 216767/Z/19/ZWellcome Trust 221890/Z/20/Z
6 · The paper itself

Abstract

backgroundCYP2C19 metabolises many medications. Its enzymatic activity can be inferred from genetic variants within CYP2C19 that link to the efficacy of drug treatments and their side effects. It is, however, unclear if enzymatic activity is associated with local or widespread differences in DNA methylation. DNA methylation differences associated with CYP2C19 metabolising status may also reveal interacting genes and pathways that underlie CYP2C19 effects on drug response and health consequences. A discovery methylome-wide association study (MWAS) was conducted in the Generation Scotland (n = 18,396) to investigate the non-linear and linear effects of CYP2C19 metaboliser status on DNA methylation. A targeted replication analysis on significant CpG sites from the discovery MWAS was conducted in Lothian Birth Cohorts of 1921 and 1936 (n = 1238). Pathway enrichment analysis was conducted for significant cytosine-guanine dinucleotide (CpG) sites. We examined whether the associations between CYP2C19 metaboliser status and DNA methylation were independent of the use of drugs that are inducers, inhibitors, or substrates of the CYP2C19 enzyme through interaction analysis.

resultsForty-eight CpG sites were significantly associated with the quadratic term of CYP2C19 metaboliser status (P

conclusionsThis research suggests that genetically-determined CYP2C19 metaboliser status is associated with both local and distal DNA methylation. These associations are independent of whether individuals were receiving drugs that are related to this enzyme.

Indexed as

Cytochrome P-450 CYP2C19DNA MethylationGenome-Wide Association StudyCpG IslandsFemaleHumansMaleScotlandCYP2C19 protein, humanCytochrome P-450 CYP2C19CYP2C19DNA methylationDrug metabolismMethylome-wide association study

Identifiers

PMID42021410
PMCPMC13251042

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