ArticleHuman molecular genetics2018
Systematic Mendelian randomization framework elucidates hundreds of CpG sites which may mediate the influence of genetic variants on disease.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- Pooled it
- Investigating causality in the association between DNA methylation and type 2 diabetes using bidirectional two-sample Mendelian randomisation.Diabetologia · 2023Pooled it
- Partitioned polygenic scores show mechanistic heterogeneity in type 2 diabetes and hypertension comorbidity.Nature communications · 2026Article
- Utilizing multimodal approach to identify candidate pathways and biomarkers and predicting frailty syndrome in individuals from UK Biobank.GeroScience · 2024Article
- Causality-enriched epigenetic age uncouples damage and adaptation.Nature aging · 2024Article
- Epigenetics insights from perceived facial aging.Clinical epigenetics · 2023Article
- Joint analysis of GWAS and multi-omics QTL summary statistics reveals a large fraction of GWAS signals shared with molecular phenotypes.Cell genomics · 2023Article
- Social Determinants of Health and Cerebral Small Vessel Disease: Is Epigenetics a Key Mediator?Journal of the American Heart Association · 2023Review
- Role of DNA methylation in the relationship between glioma risk factors and glioma incidence: a two-step Mendelian randomization study.Scientific reports · 2023Article
- Elucidating the genetic architecture of DNA methylation to identify promising molecular mechanisms of disease.Scientific reports · 2022Article
- Placental multi-omics integration identifies candidate functional genes for birthweight.Nature communications · 2022Observational
- Harnessing tissue-specific genetic variation to dissect putative causal pathways between body mass index and cardiometabolic phenotypes.American journal of human genetics · 2022Article
- Evaluating the direct effects of childhood adiposity on adult systemic metabolism: a multivariable Mendelian randomization analysis.International journal of epidemiology · 2021Article
- Cell-type-specific meQTLs extend melanoma GWAS annotation beyond eQTLs and inform melanocyte gene-regulatory mechanisms.American journal of human genetics · 2021Article
- Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.Nature genetics · 2021Article
- Causal Inference Methods to Integrate Omics and Complex Traits.Cold Spring Harbor perspectives in medicine · 2021Review
- Genetic impacts on DNA methylation: research findings and future perspectives.Genome biology · 2021Review
- Multi-omics analyses of cognitive traits and psychiatric disorders highlights brain-dependent mechanisms.Human molecular genetics · 2021Article
- Mendelian randomization integrating GWAS and mQTL data identified novel pleiotropic DNA methylation loci for neuropathology of Alzheimer's disease.Neurobiology of aging · 2021Article
- Identifying drug targets for neurological and psychiatric disease via genetics and the brain transcriptome.PLoS genetics · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
We have undertaken a systematic Mendelian randomization (MR) study using methylation quantitative trait loci (meQTL) as genetic instruments to assess the relationship between genetic variation, DNA methylation and 139 complex traits. Using two-sample MR, we identified 1148 associations across 61 traits where genetic variants were associated with both proximal DNA methylation (i.e. cis-meQTL) and complex trait variation (P < 1.39 × 10-08). Joint likelihood mapping provided evidence that the genetic variant which influenced DNA methylation levels for 348 of these associations across 47 traits was also responsible for variation in complex traits. These associations showed a high rate of replication in the BIOS QTL and UK Biobank datasets for 14 selected traits, as 101 of the attempted 128 associations survived multiple testing corrections (P < 3.91 × 10-04). Integrating expression quantitative trait loci (eQTL) data suggested that genetic variants responsible for 306 of the 348 refined meQTL associations also influence gene expression, which indicates a coordinated system of effects that are consistent with causality. CpG sites were enriched for histone mark peaks in tissue types relevant to their associated trait and implicated genes were enriched across relevant biological pathways. Though we are unable to distinguish mediation from horizontal pleiotropy in these analyses, our findings should prove valuable in prioritizing candidate loci where DNA methylation may influence traits and help develop mechanistic insight into the aetiology of complex disease.
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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 OpenQuestion graph.