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.
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There is initial evidence that alcohol use is associated with DNA methylation changes.
“There is some initial evidence to suggest that alcohol use is associated with DNAm changes (Liu et al., 2016; Wang, Xu, Zhao, Gelernter, & Zhang, 2016; Weng, Wu, Lee, Hsu, & Cheng, 2015).”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Weng, Wu, Lee, Hsu, & Cheng, 2015
Enrichment analyses of DNA methylation in alcohol users have revealed enrichment in pathways related to neural degeneration and in genes important for neurogenesis, inflammation and GABA receptors.
“Enrichment analyses examined DNAm in alcohol users have revealed enrichment in pathways related to neural degeneration (Weng et al., 2015), and in genes important for neurogenesis (NPDC1), inflammation (HERC5) and in GABA receptors (a receptor delta and B receptor subunit 1); all of which are pathways previously associated with different mental disorders, as shown in Fig. 1.”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Weng et al., 2015
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“Enrichment analyses examined DNAm in alcohol users have revealed enrichment in pathways related to neural degeneration (Weng et al., 2015), and in genes important for neurogenesis (NPDC1), inflammation (HERC5) and in GABA receptors (a receptor delta and B receptor subunit 1); all of which are pathways previously assoc…”
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Yuan, T., Tagscherer, K. E., Roth, W., Bewerunge‐Hudler, M., Brobeil, A., Kloor, M., Bläker, H., Brenner, H., & Hoffmeister, M. (2025) · International Journal of Cancer · doi:10.1002/ijc.70086
Kusuma, R. M., Lesmana, M. H. S., Amelia, V. L., Ansar, M., Wiratama, B. S., Muhtar, M. S., & Chung, M. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03596-w
- Authors
- Weng, J. T.-Y., Wu, L. S.-H., Lee, C.-S., Hsu, P. W.-C., & Cheng, A. T. A.
- Affiliations
- Yuan Ze University (TW)
- Tzu Chi University (TW)
- Mackay Memorial Hospital (TW)
- Institute of Molecular Biology, Academia Sinica (TW)
- Institute of Biomedical Sciences, Academia Sinica (TW)
- Corresponding author
- Weng, Julia Tzu-Ya
- Cheng, Andrew T.A.
- Venue
- Computers in Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 64
- Pages
- 299-306
- ISSN
- 0010-4825 (ISSN-L)
- OpenAlex
- W2108443548
- Cited by
- 37
- References
- 56
- Citations by year
- 2025: 4 · 2024: 2 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 7 · 2015: 3
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Computers in Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council, Taiwan (NSC91-2314-B-001-012, NSC92-2314-B-001-005, NSC93-2314-B-001-001, NSC94-2314-B-001-008, NSC95-2314-B-001-005, NSC96-2314-B-001-002, NSC102-2221-E-155-069)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- chronic alcohol consumption, alcoholism, DNA methylation, epigenetics, methylome, differentially methylated genes, immune response, aging, infection susceptibility, muscle contraction, neurodegeneration, neurogenesis, inflammation, HERC5, ADCY9, CKM matrix, Phox2a
- MeSH terms
- Adult, Alcoholism, Humans, Longitudinal Studies, Male, Taiwan, DNA Methylation, Epigenesis, Genetic
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