Association of PPM1G methylation with risk-taking in alcohol use disorder

Chun Il Park,Se Joo Kim,Jee In Kang,Hae Won Kim,Syung Shick Hwang

doi:10.1038/s41598-020-62504-y

Chun Il Park, Se Joo Kim + Show 3 more

Open Access

https://doi.org/10.1038/s41598-020-62504-y

Copy DOI

Journal: Scientific Reports	Publication Date: Mar 26, 2020
Citations: 1	License type: open-access

Affiliation: Yonsei University

Abstract

Alcohol use disorder (AUD) is a chronic and relapsing disease with a substantial genetic influence. Given the recent discovery of the association of PPM1G methylation with alcohol use disorder (AUD) from a genome-wide methylation study, we sought to verify and extend the previous work of AUD-related impulsivity in a Korean population with AUD. A total of 244 men with AUD were assessed for psychological characteristics and behavioral impulsivity using stop signal task (response inhibition) and Balloon Analog Risk Task (risk-taking). Leukocyte DNA methylation at PPM1G was quantified using pyrosequencing. The effects of PPM1G methylation on severity of problematic drinking measured by Alcohol Use Disorder Identification Test (AUDIT) and multidimensional impulsivity were tested using linear regression analyses. Hypermethylation of PPM1G was significantly associated with risk-taking propensity among men with AUD. No significant association of PPM1G methylation was found to be associated with AUDIT scores and response inhibition. Our findings indicate that altered methylation of PPM1G may influence the impulsive choice of risk-taking in AUD. Further research is required in order to determine the role of PPM1G in the pathophysiology of AUD and multidimensional impulsivity.

Highlights

Alcohol use disorder (AUD) is a chronic and relapsing disease with a substantial genetic influence
Among the potential associated factors selected as independent variables by the regression model, young age, long duration of AUD, higher Beck Depression Inventory (BDI) scores and presence of childhood adversity were significantly associated with higher Alcohol Use Disorder Identification Test (AUDIT) scores (Table S1)
The present study examined the role of PPM1G DNA methylation in multidimensional impulsivity among clinical samples with AUD, based on the novel finding of the PPM1G differentially methylated region from a genome-wide DNA methylation study of monozygotic twins discordant for AUD7

Summary

Introduction

Alcohol use disorder (AUD) is a chronic and relapsing disease with a substantial genetic influence. Given the recent discovery of the association of PPM1G methylation with alcohol use disorder (AUD) from a genome-wide methylation study, we sought to verify and extend the previous work of AUDrelated impulsivity in a Korean population with AUD. Childhood adversity has been reported to be associated with early initiation of alcohol[5] and higher suicidal attempts in patients with AUD6 These findings suggest that the interplay between genes and environment is involved in the pathophysiology of AUD. An endophenotype for AUD, is a multifaceted construct[8,9], we assessed multidimensional impulsivity using a self-report measure and behavioral tasks, including impulsive action of response inhibition and impulsive choice of risk-taking, and examined their associations with the PPM1G. To ascertain an unbiased effect of the PPM1G, we controlled for the effects of potential confounders such as childhood adversity on epigenetic modulation

Methods

Results

Conclusion