TY - JOUR
T1 - Opposite Epigenetic Associations With Alcohol Use and Exercise Intervention
AU - Chen, Jiayu
AU - Hutchison, Kent E.
AU - Bryan, Angela D.
AU - Filbey, Francesca M.
AU - Calhoun, Vince D.
AU - Claus, Eric D.
AU - Lin, Dongdong
AU - Sui, Jing
AU - Du, Yuhui
AU - Liu, Jingyu
N1 - Funding Information:
Funding. This project was supported by the National Institutes of Health, grant numbers P20GM103472 (to VC and JL), R01EB005846 (to VC), 1R01EB006841 (to VC), R01AA012238 (to KH), R01CA109858 (to AB), and National Science Foundation EPSCoR grant 1539067 (to VC).
Publisher Copyright:
© Copyright © 2018 Chen, Hutchison, Bryan, Filbey, Calhoun, Claus, Lin, Sui, Du and Liu.
PY - 2018/11/15
Y1 - 2018/11/15
N2 - Alcohol use disorder (AUD) is a devastating public health problem in which both genetic and environmental factors play a role. Growing evidence supports that epigenetic regulation is one major mechanism in neuroadaptation that contributes to development of AUD. Meanwhile, epigenetic patterns can be modified by various stimuli including exercise. Thus, it is an intriguing question whether exercise can lead to methylation changes that are opposite to those related to drinking. We herein conducted a comparative study to explore this issue. Three cohorts were profiled for DNA methylation (DNAm), including a longitudinal exercise intervention cohort (53 healthy participants profiled at baseline and after a 12-months exercise intervention), a cross-sectional case-control cohort (81 hazardous drinkers and 81 healthy controls matched in age and sex), and a cross-sectional binge drinking cohort (281 drinkers). We identified 906 methylation sites showing significant DNAm differences between drinkers and controls in the case-control cohort, as well as, associations with drinking behavior in the drinking cohort. In parallel, 341 sites were identified for significant DNAm alterations between baseline and follow-up in the exercise cohort. Thirty-two sites overlapped between these two set of findings, of which 15 sites showed opposite directions of DNAm associations between exercise and drinking. Annotated genes of these 15 sites were enriched in signaling pathways related to synaptic plasticity. In addition, the identified methylation sites significantly associated with impaired control over drinking, suggesting relevance to neural function. Collectively, the current findings provide preliminary evidence that exercise has the potential to partially reverse DNAm differences associated with drinking at some CpG sites, motivating rigorously designed longitudinal studies to better characterize epigenetic effects with respect to prevention and intervention of AUD.
AB - Alcohol use disorder (AUD) is a devastating public health problem in which both genetic and environmental factors play a role. Growing evidence supports that epigenetic regulation is one major mechanism in neuroadaptation that contributes to development of AUD. Meanwhile, epigenetic patterns can be modified by various stimuli including exercise. Thus, it is an intriguing question whether exercise can lead to methylation changes that are opposite to those related to drinking. We herein conducted a comparative study to explore this issue. Three cohorts were profiled for DNA methylation (DNAm), including a longitudinal exercise intervention cohort (53 healthy participants profiled at baseline and after a 12-months exercise intervention), a cross-sectional case-control cohort (81 hazardous drinkers and 81 healthy controls matched in age and sex), and a cross-sectional binge drinking cohort (281 drinkers). We identified 906 methylation sites showing significant DNAm differences between drinkers and controls in the case-control cohort, as well as, associations with drinking behavior in the drinking cohort. In parallel, 341 sites were identified for significant DNAm alterations between baseline and follow-up in the exercise cohort. Thirty-two sites overlapped between these two set of findings, of which 15 sites showed opposite directions of DNAm associations between exercise and drinking. Annotated genes of these 15 sites were enriched in signaling pathways related to synaptic plasticity. In addition, the identified methylation sites significantly associated with impaired control over drinking, suggesting relevance to neural function. Collectively, the current findings provide preliminary evidence that exercise has the potential to partially reverse DNAm differences associated with drinking at some CpG sites, motivating rigorously designed longitudinal studies to better characterize epigenetic effects with respect to prevention and intervention of AUD.
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U2 - 10.3389/fpsyt.2018.00594
DO - 10.3389/fpsyt.2018.00594
M3 - Article
AN - SCOPUS:85076282991
SN - 1664-0640
VL - 9
JO - Frontiers in Psychiatry
JF - Frontiers in Psychiatry
M1 - 594
ER -