Epigenetic profiling of DNA methylation changes associated with chronic alcohol consumption: A 12-year follow-up study

Alcoholism has always been a major public health concern in Taiwan, especially in the aboriginal communities. DNA methylation has recently been found to be associated with alcoholism. Since 1986, we have been following up on the mental health conditions of four major aboriginal peoples of Taiwan. In the current study, we attempted to profile the effect of chronic alcohol exposure on the epigenome. Clinical interviews were performed on 993 aboriginal people at phase 1 (1986), and followed up through phase 2 (1990-1992), and phase 3 (2003-2009) with DNA preparations at phases 2 and 3. Selected individuals for the present study included males from the phase 1 normal cohort who remained normal at phase 2 and became dependent on alcohol by phase 3 (n=10) and control subjects that have not had any drinking problems throughout the study (n=10). We assessed changes in DNA methylation in the blood collected at phases 2 and 3. Preliminary data show that 201 and 254 genes contain sites that are differentially methylated between the two collection time points in the control and case subjects, respectively. Among the list of genes differentially methylated in the case group, the methylation levels of 6 genes were found to correlate with alcohol consumption. These include genes involved in neurogenesis (NPDC1) and inflammation (HERC5) as well as alcoholism-associated genes ADCY9, CKM, and PHOX2A. Our study identified genes that are associated with chronic alcohol consumption at the epigenetic level. The results offer a comprehensive epigenomic map that helps enhance our understanding of alcohol-induced damages.