Journal article
DNA methylation age calculators reveal association with diabetic neuropathy in type 1 diabetes
Clinical epigenetics, Vol.12(1), pp.52-52
04/05/2020
DOI: 10.1186/s13148-020-00840-6
PMCID: PMC7132894
PMID: 32248841
Abstract
Background: Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath's four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated.
Results: Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18-20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E-3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = - 1.99, p = 0.045) and leisure time (β = - 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E-50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used.
Conclusions: Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.
Details
- Title: Subtitle
- DNA methylation age calculators reveal association with diabetic neuropathy in type 1 diabetes
- Creators
- Delnaz Roshandel - Toronto, ON CanadaZhuo Chen - Duarte, CA USAAngelo J Canty - Hamilton, ON CanadaShelley B Bull - Toronto, ON Canada Toronto, ON CanadaRama Natarajan - Duarte, CA USAAndrew D Paterson - Toronto, ON Canada Toronto, ON CanadaDiabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group
- Contributors
- L Snetselaar (Contributor) - University of Iowa, Fraternal Order of Eagles Diabetes Research Center
- Resource Type
- Journal article
- Publication Details
- Clinical epigenetics, Vol.12(1), pp.52-52
- DOI
- 10.1186/s13148-020-00840-6
- PMID
- 32248841
- PMCID
- PMC7132894
- NLM abbreviation
- Clin Epigenetics
- ISSN
- 1868-7075
- eISSN
- 1868-7083
- Publisher
- BioMed Central
- Grant note
- DP3 DK106917-01 / ;
- Language
- English
- Date published
- 04/05/2020
- Academic Unit
- Epidemiology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984215049702771
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