ArticleClinical epigenetics2021
Epigenome-wide association study of whole blood gene expression in Framingham Heart Study participants provides molecular insight into the potential role of CHRNA5 in cigarette smoking-related lung diseases.
Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 6 of them syntheses that pooled it.
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Who cites it
20 citing papers in PubMed, 6 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- The aging epigenome: integrative analyses reveal intersection with Alzheimer's disease.GeroScience · 2026Pooled it
- Methylation profile of individuals with sickle cell trait.Epigenetics · 2025Pooled it
- Pooled it
- Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis.Epigenetics · 2023Pooled it
- Epigenome-wide association study of BMI in Black populations from InterGEN and GENOA.Obesity (Silver Spring, Md.) · 2023Pooled it
- Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease.Nature communications · 2022Pooled it
- DNA methylation signature of cognitive reserve moderates CSF tau pathology in prodromal Alzheimer's disease.Research square · 2026Article
- Mitochondrial DNA copy number reduction viaEpigenomics · 2026Article
- COPD-Lung Cancer Comorbidity: Mechanistic Insights and Precision Oncology Implications.International journal of chronic obstructive pulmonary disease · 2026Review
- DNA methylation signatures of Life's Essential 8 and their implications for dementia.Alzheimer's research & therapy · 2025Article
- The association between blood-basedLung cancer management · 2025Article
- DNA methylation signature of a lifestyle-based resilience index for cognitive health.Alzheimer's research & therapy · 2025Article
- Epigenetic biomarkers of socioeconomic status are associated with age-related chronic diseases and mortality in older adults.PNAS nexus · 2025Article
- Blood DNA methylation signature for incident dementia: Evidence from longitudinal cohorts.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Smoking, blood DNA methylation sites and lung cancer risk.Environmental pollution (Barking, Essex : 1987) · 2023Article
- Expression quantitative trait methylation analysis elucidates gene regulatory effects of DNA methylation: the Framingham Heart Study.Scientific reports · 2023Article
- Epigenomic profiling of isolated blood cell types reveals highly specific B cell smoking signatures and links to disease risk.Clinical epigenetics · 2023Article
- Association of Cardiovascular Health Through Young Adulthood With Genome-Wide DNA Methylation Patterns in Midlife: The CARDIA Study.Circulation · 2022Article
- The α5-nAChR/PD-L1 axis facilitates lung adenocarcinoma cell migration and invasion.Human cell · 2022Article
- DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases.Nature communications · 2022Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundDNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases.
resultsWe performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data.
conclusionsOur results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation.
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