ArticleHuman molecular genetics2018
Deep molecular phenotypes link complex disorders and physiological insult to CpG methylation.
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 25 papers.
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Who cites it
25 citing papers in PubMed, 51 citations in OpenAlex.
- Novel approaches and applications in identifying DNA methylation markers of cardio-kidney-metabolic disease.Epigenomics · 2025Review
- Machine Learning based Model Reveals the Metabolites Involved in Coronary Artery Disease.Biomedical engineering and computational biology · 2025Article
- AutoFocus: a hierarchical framework to explore multi-omic disease associations spanning multiple scales of biomolecular interaction.Communications biology · 2024Article
- A roadmap to the molecular human linking multiomics with population traits and diabetes subtypes.Nature communications · 2024Article
- Metaboepigenetic regulation of gene expression in obesity and insulin resistance.Metabolomics : Official journal of the Metabolomic Society · 2024Article
- Genome-wide DNA methylation analysis of cannabis use disorder in a veteran cohort enriched for posttraumatic stress disorder.Psychiatry research · 2024Article
- Elucidating the role of blood metabolites on pancreatic cancer risk using two-sample Mendelian randomization analysis.International journal of cancer · 2024Article
- Genetics and Epigenetics in Obesity: What Do We Know so Far?Current obesity reports · 2023Review
- Metabolite profiles and DNA methylation in metabolic syndrome: a two-sample, bidirectional Mendelian randomization.Frontiers in genetics · 2023Article
- Genome-wide search identified DNA methylation sites that regulate the metabolome.Frontiers in genetics · 2023Article
- A biosocial return to race? A cautionary view for the postgenomic era.American journal of human biology : the official journal of the Human Biology Council · 2022Review
- Multi-Omic Approaches to Identify Genetic Factors in Metabolic Syndrome.Comprehensive Physiology · 2021Article
- Lipid Phenotypes and DNA Methylation: a Review of the Literature.Current atherosclerosis reports · 2021Review
- A Mediation Approach to Discovering Causal Relationships between the Metabolome and DNA Methylation in Type 1 Diabetes.Metabolites · 2021Article
- A prospective study of maternal adiposity and glycemic traits across pregnancy and mid-childhood metabolomic profiles.International journal of obesity (2005) · 2021Article
- The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target.International journal of molecular sciences · 2021Review
- DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures.Clinical epigenetics · 2021Article
- Genetics meets proteomics: perspectives for large population-based studies.Nature reviews. Genetics · 2021Review
- Panomics: New Databases for Advancing Cardiology.Frontiers in cardiovascular medicine · 2021Review
- Methylome-wide association study of central adiposity implicates genes involved in immune and endocrine systems.Epigenomics · 2020Article
Corrections and comments
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Authors and funding
27 authors at 7 institutions in 6 countries.
Funding
Abstract
Epigenetic regulation of cellular function provides a mechanism for rapid organismal adaptation to changes in health, lifestyle and environment. Associations of cytosine-guanine di-nucleotide (CpG) methylation with clinical endpoints that overlap with metabolic phenotypes suggest a regulatory role for these CpG sites in the body's response to disease or environmental stress. We previously identified 20 CpG sites in an epigenome-wide association study (EWAS) with metabolomics that were also associated in recent EWASs with diabetes-, obesity-, and smoking-related endpoints. To elucidate the molecular pathways that connect these potentially regulatory CpG sites to the associated disease or lifestyle factors, we conducted a multi-omics association study including 2474 mass-spectrometry-based metabolites in plasma, urine and saliva, 225 NMR-based lipid and metabolite measures in blood, 1124 blood-circulating proteins using aptamer technology, 113 plasma protein N-glycans and 60 IgG-glyans, using 359 samples from the multi-ethnic Qatar Metabolomics Study on Diabetes (QMDiab). We report 138 multi-omics associations at these CpG sites, including diabetes biomarkers at the diabetes-associated TXNIP locus, and smoking-specific metabolites and proteins at multiple smoking-associated loci, including AHRR. Mendelian randomization suggests a causal effect of metabolite levels on methylation of obesity-associated CpG sites, i.e. of glycerophospholipid PC(O-36: 5), glycine and a very low-density lipoprotein (VLDL-A) on the methylation of the obesity-associated CpG loci DHCR24, MYO5C and CPT1A, respectively. Taken together, our study suggests that multi-omics-associated CpG methylation can provide functional read-outs for the underlying regulatory response mechanisms to disease or environmental insults.
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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.