ArticleDiabetologia2016
Tobacco smoking is associated with DNA methylation of diabetes susceptibility genes.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Pooled it
- Examining the potential causal relationships among smoking, blood DNA methylation, and type 2 diabetes development: A Mendelian randomization study.Tobacco induced diseases · 2026Article
- Phenotype prediction using biologically interpretable neural networks on multi-cohort multi-omics data.NPJ systems biology and applications · 2024Article
- Multiomics Data Analysis Identified CpG Sites That Mediate the Impact of Smoking on Cardiometabolic Traits.Epigenomes · 2023Article
- Dissecting the epigenomic differences between smoking and nicotine dependence in a veteran cohort.Addiction biology · 2023Article
- Mechanisms Linking COPD to Type 1 and 2 Diabetes Mellitus: Is There a Relationship between Diabetes and COPD?Medicina (Kaunas, Lithuania) · 2022Review
- Review
- Relationship BetweenPharmacogenomics and personalized medicine · 2021Article
- Smoking-related changes in DNA methylation and gene expression are associated with cardio-metabolic traits.Clinical epigenetics · 2020Article
- Association of common gene-smoking interactions with elevated plasma apolipoprotein B concentration.Lipids in health and disease · 2020Article
- Objectives, design and main findings until 2020 from the Rotterdam Study.European journal of epidemiology · 2020Article
- Association of smoking habits with TXNIP DNA methylation levels in leukocytes among general Japanese population.PloS one · 2020Article
- Pleiotropic Effects of a KCNQ1 Variant on Lipid Profiles and Type 2 Diabetes: A Family-Based Study in China.Journal of diabetes research · 2020Article
- Multi-Omics Analysis Reveals MicroRNAs Associated With Cardiometabolic Traits.Frontiers in genetics · 2020Article
- DNA methylation is associated with lung function in never smokers.Respiratory research · 2019Article
- Validated inference of smoking habits from blood with a finite DNA methylation marker set.European journal of epidemiology · 2019Article
- Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression.Human molecular genetics · 2019Article
- Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism.International journal of molecular sciences · 2018Review
- An integrated -omics analysis of the epigenetic landscape of gene expression in human blood cells.BMC genomics · 2018Article
- Understanding the role of the chromosome 15q25.1 in COPD through epigenetics and transcriptomics.European journal of human genetics : EJHG · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisTobacco smoking, a risk factor for diabetes, is an established modifier of DNA methylation. We hypothesised that tobacco smoking modifies DNA methylation of genes previously identified for diabetes.
methodsWe annotated CpG sites available on the Illumina Human Methylation 450K array to diabetes genes previously identified by genome-wide association studies (GWAS), and investigated them for an association with smoking by comparing current to never smokers. The discovery study consisted of 630 individuals (Bonferroni-corrected p = 1.4 × 10(-5)), and we sought replication in an independent sample of 674 individuals. The replicated sites were tested for association with nearby genetic variants and gene expression and fasting glucose and insulin levels.
resultsWe annotated 3,620 CpG sites to the genes identified in the GWAS on type 2 diabetes. Comparing current smokers to never smokers, we found 12 differentially methylated CpG sites, of which five replicated: cg23161492 within ANPEP (p = 1.3 × 10(-12)); cg26963277 (p = 1.2 × 10(-9)), cg01744331 (p = 8.0 × 10(-6)) and cg16556677 (p = 1.2 × 10(-5)) within KCNQ1 and cg03450842 (p = 3.1 × 10(-8)) within ZMIZ1. The effect of smoking on DNA methylation at the replicated CpG sites attenuated after smoking cessation. Increased DNA methylation at cg23161492 was associated with decreased gene expression levels of ANPEP (p = 8.9 × 10(-5)). rs231356-T, which was associated with hypomethylation of cg26963277 (KCNQ1), was associated with a higher odds of diabetes (OR 1.06, p = 1.3 × 10(-5)). Additionally, hypomethylation of cg26963277 was associated with lower fasting insulin levels (p = 0.04). CONCLUSIONS/
interpretationTobacco smoking is associated with differential DNA methylation of the diabetes risk genes ANPEP, KCNQ1 and ZMIZ1. Our study highlights potential biological mechanisms connecting tobacco smoking to excess risk of type 2 diabetes.
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