Dataset Information

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

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.

SUBMITTER: Park CI

PROVIDER: S-EPMC7099006 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Park Chun Il CI Kim Hae Won HW Hwang Syung Shick SS Kang Jee In JI Kim Se Joo SJ

Scientific reports 20200326 1

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 Ba ...[more]

PMID: 32218500

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Project description:<p>The Australian twin-family study of alcohol use disorder (OZALC study) derives from telephone diagnostic interview studies of two general population volunteer cohorts of Australian twins (cohort 1, mostly born 1940-1964; cohort 2, born 1964-71) and the spouses of the former cohort - a total of over 11,000 families. Three coordinated studies, using a shared assessment protocol and with a shared goal of gene-discovery, were conducted - one funded by the National Institute on Drug Abuse, the others by the National Institute on Alcoholism and Alcohol Abuse - by investigators associated with the Midwest Alcoholism Research Center at Washington University in St. Louis, and investigators at Queensland Institute of Medical Research, Brisbane, Australia (led by Professor Nicholas Martin), using informative families identified from these cohorts. The first of these (NIDA Nicotine Addiction Genetics [NAG] project, PI Pamela Madden) identified index cases from the 3 cohorts with a history of heavy smoking (smoked 20 or more cigarettes daily, or 40 or more cigarettes on 1 or more occasions) and with additional available full siblings who were smokers, and interviewed and obtained blood samples from twins, and cooperative full siblings and parents, in order to identify families that would be informative for linkage analysis of a quantitative heaviness of smoking trait. The second identified additional families with an index case who either reported a history of alcohol dependence (DSM-IV), or scored above the 85th percentile on a quantitative measure of heaviness of alcohol use (alcohol factor score), derived from measures of frequency of heavy drinking, frequency of drinking to intoxication, and typical weekly consumption in standard drinks (all referenced to the respondent's heaviest drinking period) and of lifetime maximum 1-day alcohol consumption and maximum tolerance to alcohol (drinks before getting drunk or before feeling effects of alcohol). Interview and DNA were obtained from index cases and siblings, and DNA only from available parents. The goal of this second study (NIAAA OZ-ALCOHOL EDAC study, PI Andrew Heath) was to identify sibships including pairs who were either extreme concordant for the quantitative consumption measure (both scoring above the 85th percentile) or extreme discordant (one scoring above the 85th percentile and one scoring below the 30th percentile) that would be informative for linkage analysis. The third identified additional sibships solely on the basis of large sibship size, regardless of alcohol or tobacco use phenotypes (NIAAA OZ-BIGSIB study, PIs the late Richard Todd, Andrew Heath). From these coordinated studies a case-control series of alcohol dependent individuals and unaffected controls were constructed for a family-based Genomewide Association Study (OZALC-GWAS) of heaviness of alcohol use and alcohol dependence, funded by the National Institute of Alcoholism and Alcohol Abuse. These data are made available here for all investigators studying outcomes related to alcohol or tobacco use (including major depressive disorder).</p>

Project description:BackgroundExtensive research indicates that having a positive family history of alcohol use disorder (FHP) and impulsivity are 2 risk factors for problem drinking. To our knowledge, no study has investigated which facets of impulsivity interact with family history to increase risk for problem drinking. The goal of this study was to: (i) examine whether FHP individuals with higher levels of impulsivity are more likely to engage in problematic drinking, and (ii) identify which facets of impulsivity interact with FHP to increase risk for problems.MethodsThe data consisted of a combined sample of 757 participants (50% female, 73% White, mean age = 32.85, SD = 11.31) drawn from the Transdisciplinary Tobacco Use Research Center and the Center for the Translational Neuroscience of Alcohol. Analyses of covariance and cumulative logistic regression models investigated the association of family history and impulsivity-related traits with drinking quantity, frequency, and alcohol-related problems. Models were adjusted for age, sex, race, ethnic group, education level, and data source.ResultsSignificant interactions between impulsivity and family history were found for measures of alcohol-related problems. Specifically, there was a stronger positive association of Barratt Impulsiveness Scale (BIS) poor self-regulation with interpersonal, F(1, 504) = 6.27, p = 0.01, and impulse control alcohol-related problems, F(1, 504) = 6.00, p = 0.01, among FHP compared to FHN individuals. Main effects of family history and impulsivity on alcohol quantity and frequency of use and problems were also found.ConclusionsThese findings suggest that having both a family history of AUD and high BIS poor self-regulation is more strongly associated with alcohol-related consequences in the interpersonal and impulse control domains. Given the heterogeneity of impulsivity, these findings highlight the need for additional research to examine which facets of impulsivity are associated with which alcohol outcomes to narrow phenotypic risk for alcohol misuse.

Dataset Information

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

Publications

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

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