ArticlePLoS genetics2017
The relative contribution of DNA methylation and genetic variants on protein biomarkers for human diseases.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Animal and plant protein intake during infancy and childhood DNA methylation: a meta-analysis in the NutriPROGRAM consortium.Epigenetics · 2024Pooled it
- Soluble CD14-associated DNA methylation sites predict mortality among men with HIV infection.AIDS (London, England) · 2022Pooled it
- A machine learning approach to identify key epigenetic transcripts for ageing research in human blood (Epitage).Biogerontology · 2026Article
- Epigenome-wide association study of blood proteome in the Atherosclerosis Risk in Communities study.HGG advances · 2026Article
- Association Between Personal, Behavioral, Psychological, Biochemical and Molecular Biomarkers with Illness Count in a Sample of Mexican Individuals.International journal of molecular sciences · 2026Article
- ModSeqR: an R package for efficient analysis of modified nucleotide data.BMC genomics · 2026Article
- MAJA: multivariate Bayesian model for discovery of shared epigenetic pathways across human phenotypes.Bioinformatics advances · 2026Article
- DNA Methylation Status of Regulatory Regions of Apoptosis-Associated Genes in Dystropy «Huntington's Disease-Non-Small Cell Lung Cancer».Epigenomes · 2025Article
- A multi-trait epigenome-wide association study identified DNA methylation signature of inflammation among men with HIV.Clinical epigenetics · 2024Article
- DNA Methylation at C-Reactive Protein-Associated CpG Sites May Mediate the Pathway Between Educational Attainment and Cognition.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- A multi-trait epigenome-wide association study identified DNA methylation signature of inflammation among people with HIV.Research square · 2024Article
- Cell-type specific methylation changes in the newborn child associated to obstetric pain relief.PloS one · 2024Article
- New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine.Cellular & molecular immunology · 2023Review
- Integrating Common Risk Factors with Polygenic Scores Improves the Prediction of Type 2 Diabetes.International journal of molecular sciences · 2023Article
- A Polynesian-specific copy number variant encompassing the MICA gene associates with gout.Human molecular genetics · 2022Article
- Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability.Nature communications · 2022Article
- Epigenome-wide scan identifies differentially methylated regions for lung cancer using pre-diagnostic peripheral blood.Epigenetics · 2022Article
- Genome- and epigenome-wide studies of plasma protein biomarkers for Alzheimer's disease implicate TBCA and TREM2 in disease risk.Alzheimer's & dementia (Amsterdam, Netherlands) · 2022Article
- Methylation-derived inflammatory measures and lung cancer risk and survival.Clinical epigenetics · 2021Article
- Causal effects of inflammatory protein biomarkers on inflammatory diseases.Science advances · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Associations between epigenetic alterations and disease status have been identified for many diseases. However, there is no strong evidence that epigenetic alterations are directly causal for disease pathogenesis. In this study, we combined SNP and DNA methylation data with measurements of protein biomarkers for cancer, inflammation or cardiovascular disease, to investigate the relative contribution of genetic and epigenetic variation on biomarker levels. A total of 121 protein biomarkers were measured and analyzed in relation to DNA methylation at 470,000 genomic positions and to over 10 million SNPs. We performed epigenome-wide association study (EWAS) and genome-wide association study (GWAS) analyses, and integrated biomarker, DNA methylation and SNP data using between 698 and 1033 samples depending on data availability for the different analyses. We identified 124 and 45 loci (Bonferroni adjusted P < 0.05) with effect sizes up to 0.22 standard units' change per 1% change in DNA methylation levels and up to four standard units' change per copy of the effective allele in the EWAS and GWAS respectively. Most GWAS loci were cis-regulatory whereas most EWAS loci were located in trans. Eleven EWAS loci were associated with multiple biomarkers, including one in NLRC5 associated with CXCL11, CXCL9, IL-12, and IL-18 levels. All EWAS signals that overlapped with a GWAS locus were driven by underlying genetic variants and three EWAS signals were confounded by smoking. While some cis-regulatory SNPs for biomarkers appeared to have an effect also on DNA methylation levels, cis-regulatory SNPs for DNA methylation were not observed to affect biomarker levels. We present associations between protein biomarker and DNA methylation levels at numerous loci in the genome. The associations are likely to reflect the underlying pattern of genetic variants, specific environmental exposures, or represent secondary effects to the pathogenesis of disease.
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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.