SynthesisPloS one2017
Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes.
Synthesis in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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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.
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.
Who cites it
5 citing papers in PubMed, 13 citations in OpenAlex.
- Comprehensive Analysis Based on Genes Associated With Cuproptosis, Ferroptosis, and Pyroptosis for the Prediction of Diagnosis and Therapies in Coronary Artery Disease.Cardiovascular therapeutics · 2025Article
- Revisiting genetic artifacts on DNA methylation microarrays exposes novel biological implications.Genome biology · 2021Article
- Dysregulation of Epigenetic Mechanisms of Gene Expression in the Pathologies of Hyperhomocysteinemia.International journal of molecular sciences · 2019Review
- Quantitative DNA Methylation Analysis of DLGAP2 Gene using Pyrosequencing in Schizophrenia with Tardive Dyskinesia: A Linear Mixed Model Approach.Scientific reports · 2018Article
- Association ofFrontiers in aging neuroscience · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
39 authors at 13 institutions in 7 countries.
Funding
Abstract
backgroundDNA methylation is affected by the activities of the key enzymes and intermediate metabolites of the one-carbon pathway, one of which involves homocysteine. We investigated the effect of the well-known genetic variant associated with mildly elevated homocysteine: MTHFR 677C>T independently and in combination with other homocysteine-associated variants, on genome-wide leukocyte DNA-methylation.
methodsMethylation levels were assessed using Illumina 450k arrays on 9,894 individuals of European ancestry from 12 cohort studies. Linear-mixed-models were used to study the association of additive MTHFR 677C>T and genetic-risk score (GRS) based on 18 homocysteine-associated SNPs, with genome-wide methylation.
resultsMeta-analysis revealed that the MTHFR 677C>T variant was associated with 35 CpG sites in cis, and the GRS showed association with 113 CpG sites near the homocysteine-associated variants. Genome-wide analysis revealed that the MTHFR 677C>T variant was associated with 1 trans-CpG (nearest gene ZNF184), while the GRS model showed association with 5 significant trans-CpGs annotated to nearest genes PTF1A, MRPL55, CTDSP2, CRYM and FKBP5.
conclusionsOur results do not show widespread changes in DNA-methylation across the genome, and therefore do not support the hypothesis that mildly elevated homocysteine is associated with widespread methylation changes in leukocytes.
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Registered trials
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.