DNA methylation age is accelerated in alcohol dependence

Abstract

Alcohol dependence (ALC) is a chronic, relapsing disorder that increases the burden of chronic disease and significantly contributes to numerous premature deaths each year. Previous research suggests that chronic, heavy alcohol consumption is associated with differential DNA methylation patterns. In addition, DNA methylation levels at certain CpG sites have been correlated with age. We used an epigenetic clock to investigate the potential role of excessive alcohol consumption in epigenetic aging. We explored this question in five independent cohorts, including DNA methylation data derived from datasets from blood (n = 129, n = 329), liver (n = 92, n = 49), and postmortem prefrontal cortex (n = 46). One blood dataset and one liver tissue dataset of individuals with ALC exhibited positive age acceleration (p < 0.0001 and p = 0.0069, respectively), whereas the other blood and liver tissue datasets both exhibited trends of positive age acceleration that were not significant (p = 0.83 and p = 0.57, respectively). Prefrontal cortex tissue exhibited a trend of negative age acceleration (p = 0.19). These results suggest that excessive alcohol consumption may be associated with epigenetic aging in a tissue-specific manner and warrants further investigation using multiple tissue samples from the same individuals.

Fig. 1. Age acceleration in blood.

(a) NIAAA blood sample. (b) Grady Trauma Project (GSE72680) blood sample. Bar plots show average age acceleration and 1 SE, as reported in Table 2. Scatter plots show chronological age vs. DNA methylation age and a line in which DNA methylation age was regressed on chronological age. Points lying above the line exhibit negative age acceleration and points lying below the line exhibit positive age acceleration. In both samples, age acceleration was positive in cases and negative in controls. Average age acceleration differed significantly (p < 0.0001) between cases and controls in the NIAAA sample, but not in the Grady Trauma Project sample

Fig. 2. Age acceleration in liver and prefrontal cortex.

(a) UMN liver sample. (b) Mayo Clinic liver sample (GSE60753). (c) Australian Brain Bank (GSE49393) prefrontal cortex sample. Bar plots show average age acceleration and 1 SE, as reported in Table 2. Scatter plots show chronological age vs. DNA methylation age and a line in which DNA methylation age was regressed on chronological age. Points lying above the line exhibit negative age acceleration and points lying below the line exhibit positive age acceleration. In liver samples, age acceleration was positive in cases and negative in controls. Average age acceleration differed significantly (p = 0.0069) between cases and controls in the UMN sample, but not in the Mayo Clinic Sample. In prefrontal cortex, age acceleration was negative in cases and positive in controls. Average age acceleration did not differ significantly between cases and controls