ArticleNature genetics2017
Disease variants alter transcription factor levels and methylation of their binding sites.
Abstract read
In one paragraph
Article in Nature genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 293 papers, 20 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
293citing papers in PubMed, 20 pooled it
–field-weighted citation impact
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.
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
293 citing papers in PubMed, 20 syntheses or guidelines pooled it.
- Epigenome-wide association study meta-analysis of wellbeing.Clinical epigenetics · 2026Pooled it
- Epigenome-wide association study of circulating interleukin-6 connects DNA methylation to immunometabolic and inflammatory health.Communications biology · 2026Pooled it
- DNA methylation of genes involved in lipid metabolism drives adiponectin levels and metabolic disease.Diabetologia · 2026Pooled it
- Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking.Nature communications · 2025Pooled it
- Genome-Wide Interaction Analyses of Serum Calcium on Ventricular Repolarization Time in 125 393 Participants.Journal of the American Heart Association · 2024Pooled it
- Epigenome-wide association study of dietary fatty acid intake.Clinical epigenetics · 2024Pooled it
- Investigating causality in the association between DNA methylation and type 2 diabetes using bidirectional two-sample Mendelian randomisation.Diabetologia · 2023Pooled it
- DNA methylation analysis is used to identify novel genetic loci associated with circulating fibrinogen levels in blood.Journal of thrombosis and haemostasis : JTH · 2023Pooled it
- Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease.Nature communications · 2022Pooled it
- Pulmonary Function and Blood DNA Methylation: A Multiancestry Epigenome-Wide Association Meta-analysis.American journal of respiratory and critical care medicine · 2022Pooled it
- Genome-wide association studies identify novel genetic loci for epigenetic age acceleration among survivors of childhood cancer.Genome medicine · 2022Pooled it
- Epigenome-wide meta-analysis of PTSD symptom severity in three military cohorts implicates DNA methylation changes in genes involved in immune system and oxidative stress.Molecular psychiatry · 2022Pooled it
- Methylome-wide association study of antidepressant use in Generation Scotland and the Netherlands Twin Register implicates the innate immune system.Molecular psychiatry · 2022Pooled it
- DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.Molecular psychiatry · 2021Pooled it
- Genetic basis of lacunar stroke: a pooled analysis of individual patient data and genome-wide association studies.The Lancet. Neurology · 2021Pooled it
- Pooled it
- Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders.Genome biology · 2021Pooled it
- Shared DNA methylation signatures in childhood allergy: The MeDALL study.The Journal of allergy and clinical immunology · 2021Pooled it
- DNA methylation of blood cells is associated with prevalent type 2 diabetes in a meta-analysis of four European cohorts.Clinical epigenetics · 2021Pooled it
- The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis.Nature communications · 2020Pooled it
233 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
56 authors.
Marc Jan BonderUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
René LuijkMolecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
Daria V ZhernakovaUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Matthijs MoedMolecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
Patrick DeelenUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.ORCID 0000-0002-5654-3966
Martijn VermaatDepartment of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Maarten van ItersonMolecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
Freerk van DijkUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Michiel van GalenUniversity of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, the Netherlands.
Jan BotSURFsara, Amsterdam, the Netherlands.
Roderick C SliekerMolecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.ORCID 0000-0003-0961-9152
P Mila JhamaiDepartment of Internal Medicine, ErasmusMC, Rotterdam, the Netherlands.
Michael VerbiestUniversity of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, the Netherlands.
H Eka D SuchimanMolecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.ORCID 0000-0002-7168-5516
Marijn VerkerkDepartment of Internal Medicine, ErasmusMC, Rotterdam, the Netherlands.
Ruud van der BreggenMolecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
Jeroen van RooijDepartment of Internal Medicine, ErasmusMC, Rotterdam, the Netherlands.
Nico LakenbergMolecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
Wibowo ArindrartoMedical Statistics Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
Szymon M KielbasaSequence Analysis Support Core, Leiden University Medical Center, Leiden, the Netherlands.
Iris JonkersUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Peter van 't HofSequence Analysis Support Core, Leiden University Medical Center, Leiden, the Netherlands.
Irene NoorenSURFsara, Amsterdam, the Netherlands.
Marian BeekmanMolecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.ORCID 0000-0003-0585-6206
Joris DeelenMolecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.ORCID 0000-0003-4483-3701
Diana van HeemstDepartment of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
Alexandra ZhernakovaUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.ORCID 0000-0002-4574-0841
Ettje F TigchelaarUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Morris A SwertzUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Albert HofmanDepartment of Epidemiology, ErasmusMC, Rotterdam, the Netherlands.
André G UitterlindenDepartment of Internal Medicine, ErasmusMC, Rotterdam, the Netherlands.
René PoolDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0001-5579-0933
Jenny van DongenDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
Jouke J HottengaDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
Coen D A StehouwerDepartment of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
Carla J H van der KallenDepartment of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
Casper G SchalkwijkDepartment of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
Leonard H van den BergDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Erik W van ZwetMedical Statistics Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
Hailiang MeiSequence Analysis Support Core, Leiden University Medical Center, Leiden, the Netherlands.
Yang LiUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Mathieu LemireOntario Institute for Cancer Research, Toronto, Ontario, Canada.
Thomas J HudsonOntario Institute for Cancer Research, Toronto, Ontario, Canada.ORCID 0000-0002-1376-4849
BIOS Consortium
P Eline SlagboomMolecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
Cisca WijmengaUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Jan H VeldinkDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Marleen M J van GreevenbroekDepartment of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
Cornelia M van DuijnGenetic Epidemiology Unit, Department of Epidemiology, ErasmusMC, Rotterdam, the Netherlands.
Dorret I BoomsmaDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
Aaron IsaacsSchool for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, Maastricht, the Netherlands.ORCID 0000-0001-5037-4834
Rick JansenDepartment of Psychiatry, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0002-3333-6737
Joyce B J van MeursDepartment of Internal Medicine, ErasmusMC, Rotterdam, the Netherlands.
Peter A C 't HoenDepartment of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Lude FrankeUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.ORCID 0000-0002-5159-8802
Bastiaan T HeijmansMolecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most disease-associated genetic variants are noncoding, making it challenging to design experiments to understand their functional consequences. Identification of expression quantitative trait loci (eQTLs) has been a powerful approach to infer the downstream effects of disease-associated variants, but most of these variants remain unexplained. The analysis of DNA methylation, a key component of the epigenome, offers highly complementary data on the regulatory potential of genomic regions. Here we show that disease-associated variants have widespread effects on DNA methylation in trans that likely reflect differential occupancy of trans binding sites by cis-regulated transcription factors. Using multiple omics data sets from 3,841 Dutch individuals, we identified 1,907 established trait-associated SNPs that affect the methylation levels of 10,141 different CpG sites in trans (false discovery rate (FDR) < 0.05). These included SNPs that affect both the expression of a nearby transcription factor (such as NFKB1, CTCF and NKX2-3) and methylation of its respective binding site across the genome. Trans methylation QTLs effectively expose the downstream effects of disease-associated variants.
Indexed as
DNA MethylationGene Expression RegulationQuantitative Trait LociBinding SitesCohort StudiesDiseaseFemaleGenome, HumanGenome-Wide Association StudyHumansMaleMiddle AgedPhenotypePolymorphism, Single NucleotideTranscription FactorsTranscription Factors
Identifiers
PMID
27918535What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
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.