Type 2 diabetes and leucocyte DNA methylation: an epigenome-wide association study in over 1,500 older adults

Florath, Ines; Butterbach, Katja; Heiss, Jonathan; Bewerunge-Hudler, Melanie; Zhang, Yan; Schöttker, Ben; Brenner, Hermann

doi:10.1007/s00125-015-3773-7

Cited by 115 publications

(109 citation statements)

References 42 publications

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“…As previously described [50], samples were analyzed following the manufacturer's instruction at the Genomics and Proteomics Core Facility of the German Cancer Research Center, Heidelberg, Germany. Illumina'sGenomeStudio ® (version 2011.1; Illumina.Inc.)…”

Section: Methodsmentioning

confidence: 99%

Relationship of tobacco smoking and smoking-related DNA methylation with epigenetic age acceleration

et al. 2016

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Recent studies have identified biomarkers of chronological age based on DNA methylation levels. Since active smoking contributes to a wide spectrum of aging-related diseases in adults, this study intended to examine whether active smoking exposure could accelerate the DNA methylation age in forms of age acceleration (AA, residuals of the DNA methylation age estimate regressed on chronological age). We obtained the DNA methylation profiles in whole blood samples by Illumina Infinium Human Methylation450 Beadchip array in two independent subsamples of the ESTHER study and calculated their DNA methylation ages by two recently proposed algorithms. None of the self-reported smoking indicators (smoking status, cumulative exposure and smoking cessation time) or serum cotinine levels was significantly associated with AA. On the contrary, we successfully confirmed that 66 out of 150 smoking-related CpG sites were associated with AA, even after correction for multiple testing (FDR <0.05). We further built a smoking index (SI) based on these loci and demonstrated a monotonic dose-response relationship of this index with AA. In conclusion, DNA methylation-based biological indicators for current and past smoking exposure, but not self-reported smoking information or serum cotinine levels, were found to be related to DNA methylation defined AA. Further research should address potential mechanisms underlying the observed patterns, such as potential reflections of susceptibility to environmental hazards in both smoking related methylation changes and methylation defined AA.

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Section: Methodsmentioning

confidence: 99%

Relationship of tobacco smoking and smoking-related DNA methylation with epigenetic age acceleration

et al. 2016

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“…As previously described [31], samples were analyzed following the manufacturer's instruction at the Genomics and Proteomics Core Facility of the German Cancer Research Center, Heidelberg, Germany. Illumina's GenomeStudio Ò (version 2011.1; Illumina, Inc.) was employed to extract DNA methylation signals from the scanned arrays (Module version 1.9.0; Illumina, Inc.).…”

Section: Laboratory Analysesmentioning

confidence: 99%

Associations of self-reported smoking, cotinine levels and epigenetic smoking indicators with oxidative stress among older adults: a population-based study

et al. 2017

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Tobacco smoking and oxidative stress (OS) are both related to a wide spectrum of adverse age-related health outcomes, but their association is not yet well-established. We examined the associations of self-reported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with two urinary proxy markers of OS, 8-isoprostane (8-iso) and 8-hydroxy-2'-deoxyguanosine (8-oxodG), in two independent subsets of older adults recruited in Germany (discovery set: n = 978, validation set: n = 531). We obtained DNA methylation profiles in whole blood samples by Illumina Human Methylation450K Beadchip and measured the urinary levels of both OS markers using commercial ELISA kits. After controlling for potential confounders, current smoking, cumulative smoking exposure (pack-years) and serum cotinine levels (ng/ml) were strongly associated with 8-iso levels (p values <0.0001, 0.004 and 0.001, respectively). Of 151 previously identified smoking-related CpG sites, 71 loci were associated with 8-iso levels after correction for multiple testing (FDR < 0.05) in the validation phase and were designated as loci related to 8-iso levels defined OS. In addition, serum cotinine levels, cumulative smoking exposure and a smoking index (SI) based on the 71 identified loci manifested monotonic associations with 8-iso levels. However, we did not observe any associations between these smoking indicators and 8-oxodG levels. In conclusion, this study suggests that smoking-related epigenetic alterations are closely correlated with smoking-induced OS. The identified CpG sites could potentially be prognostic epigenetic markers of OS and OS-related health outcomes. Our findings and the underlying mechanisms should be followed up in further, preferably longitudinal studies.

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“…55 DNA methylation profiles of 151 smoking-related loci which had been identified 2 times in previous smoking EWAS 26 were extracted by the Illumina HumanMethylation450 BeadChip (Illumina, San Diego, CA, USA). As described previously,, 56 samples were analyzed following the manufacturer's instruction at the Genomics and Proteomics Core Facility of the German Cancer Research Center, Heidelberg, Germany. Illumina's GenomeStudio Ò (version 2,011.1; Illumina Inc.) was used to extract DNA methylation signals from the scanned arrays (Module version 1.9.0; Illumina Inc.).…”

Section: Laboratory Analysesmentioning

confidence: 99%

Tobacco smoking and smoking-related DNA methylation are associated with the development of frailty among older adults

et al. 2017

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Tobacco smoking is a preventable environmental factor that contributes to a wide spectrum of age-related health outcomes; however, its association with the development of frailty is not yet well established. We examined the associations of self-reported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with a quantitative frailty index (FI) in 2 independent subsets of older adults (age 50-75) recruited in Saarland, Germany in 2000 -2002 (discovery set: n D 978, validation set: n D 531). We obtained DNA methylation profiles in whole blood samples by Illumina HumanMethylation450 BeadChip and calculated the FI according to the method of Mitnitski and Rockwood. Mixed linear regression models were implemented to assess the associations between smoking indicators and the FI. After controlling for potential covariates, current smoking, cumulative smoking exposure (pack-years), and time after smoking cessation (years) were significantly associated with the FI (P-value < 0.05). In the discovery panel, 17 out of 151 previously identified smoking-related CpG sites were associated with the FI after correction for multiple testing (FDR < 0.05). Nine of them survived in the validation phase and were designated as frailty-associated loci. A smoking index (SI) based on the 9 loci manifested a monotonic association with the FI. In conclusion, this study suggested that epigenetic alterations could play a role in smoking-associated development of frailty. The identified CpG sites have the potential to be prognostic biomarkers of frailty and frailty-related health outcomes. Our findings and the underlying mechanisms should be followed up in further, preferably longitudinal studies.

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Type 2 diabetes and leucocyte DNA methylation: an epigenome-wide association study in over 1,500 older adults

Cited by 115 publications

References 42 publications

Relationship of tobacco smoking and smoking-related DNA methylation with epigenetic age acceleration

Relationship of tobacco smoking and smoking-related DNA methylation with epigenetic age acceleration

Associations of self-reported smoking, cotinine levels and epigenetic smoking indicators with oxidative stress among older adults: a population-based study

Tobacco smoking and smoking-related DNA methylation are associated with the development of frailty among older adults

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