Abstract
DNA methylation-based clocks provide the most accurate age estimates with practical implications for clinical and forensic genetics. However, the effects of external factors that may influence the estimates are poorly studied. Here, we evaluated the effect of alcohol consumption on epigenetic age prediction in a cohort of extreme alcohol abusers. Blood samples from deceased alcohol abusers and age- and sex-matched controls were analyzed using the VISAGE enhanced tool for age prediction from somatic tissues that enables examination of 44 CpGs within eight age markers. Significantly altered DNA methylation was recorded for alcohol abusers in MIR29B2CHG. This resulted in a mean predicted age of 1.4 years higher compared to the controls and this trend increased in older individuals. The association of alcohol abuse with epigenetic age acceleration, as determined by the prediction analysis performed based on MIR29B2CHG, was small but significant (β = 0.190; P-value = 0.007). However, the observed alteration in DNA methylation of MIR29B2CHG had a non-significant effect on age estimation with the VISAGE age prediction model. The mean absolute error in the alcohol-abusing cohort was 3.1 years, compared to 3.3 years in the control group. At the same time, upregulation of MIR29B2CHG expression may have a biological function, which merits further studies.
Highlights
DNA methylation (DNAm) is an epigenetic modification involved in the regulation of gene expression and processes responsible for normal organism development and growth, including genome imprinting and X chromosome inactivation
The Visible Attributes through Genomics (VISAGE) Age Tool targets eight well-validated DNA methylation markers (ELOVL2, MIR29B2CHG, KLF14, FHL2, TRIM59, PDE4C, EDARADD, and ASPA), of which 6 CpG sites are included in the age estimation model for blood
Considering that excessive alcohol abusers may have different levels of methylation compared to healthy controls, we examined whether severe alcohol consumption might be associated with accelerated aging and increased error of age estimation using the VISAGE Age Tool
Summary
DNA methylation (DNAm) is an epigenetic modification involved in the regulation of gene expression and processes responsible for normal organism development and growth, including genome imprinting and X chromosome inactivation. The blood model explains 98.2% of the age-related variance and predicts age with a mean absolute error (MAE) of 3.2 years [22] The usefulness of this tool in forensics is due to the high sensitivity of DNA methylation measurements using multiplexed targeted massively parallel sequencing (MPS), which provides good accuracy of chronological age prediction. Validation of this method should include an assessment of the effect of potential confounders on age estimation. Considering that excessive alcohol abusers may have different levels of methylation compared to healthy controls, we examined whether severe alcohol consumption might be associated with accelerated aging and increased error of age estimation using the VISAGE Age Tool. Our objective was to track potential dysregulation of DNA methylation in blood through excessive alcohol abuse at the eight markers used for forensic chronological age estimation
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