title: Integrative epigenetic profiling analysis identifies DNA methylation changes associated with chronic alcohol consumption.
abstract: Alcoholism has always been a major public health concern in Taiwan, especially in the aboriginal communities. Emerging evidence supports the association between DNA methylation and alcoholism, though very few studies have examined the effect of chronic alcohol consumption on the epignome. Since 1986, we have been following up on the mental health conditions of four major aboriginal peoples of Taiwan. The 993 aboriginal people who underwent the phase 1 (1986) clinical interviews were followed up through phase 2 (1990-1992), and phase 3 (2003-2009). Selected individuals for the current study included 10 males from the phase 1 normal cohort who remained normal at phase 2 and became dependent on alcohol by phase 3 and 10 control subjects who have not had any drinking problems throughout the study. We profiled the DNA methylation changes in the blood samples collected at phases 2 and 3. Enrichment analyses have identified several biological processes related to immune system responses and aging in the control group. In contrast, differentially methylated genes in the case group were mostly associated with susceptibility to infections, as well as pathways related to muscular contraction and neural degeneration. The methylation levels of six 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. Given the limited sample size, our approach uncovered genes and disease pathways associated with chronic alcohol consumption at the epigenetic level. The results offer a preliminary methylome map that enhances our understanding of alcohol-induced damages and offers new targets for alcohol injury research.
authors.affiliation: Department of Computer Science & Engineering, Yuan Ze University, Chung-Li, Taiwan; Innovation Center for Big Data and Digital Convergence, Yuan Ze University, Chung-Li, Taiwan. Electronic address: julweng@saturn.yzu.edu.tw.
authors.forename: Julia Tzu-Ya
authors.initials: JT
authors.lastname: Weng
authors.affiliation: Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
authors.forename: Lawrence Shih-Hsin
authors.initials: LS
authors.lastname: Wu
authors.affiliation: Department of Psychiatry, Mackay Memorial Hospital, New Taipei City, Taiwan.
authors.forename: Chau-Shoun
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Bioinformatics Core Laboratory, Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Paul Wei-Che
authors.initials: PW
authors.lastname: Hsu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Andrew T A
authors.initials: AT
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D013624:Taiwan
keywords: Alcoholism; DNA methylation; Epigenetic profiling; Longitudinal study; Taiwanese aboriginals