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Genome-Wide Association Study Meta-Analysis of the Alcohol Use Disorders Identification Test (AUDIT) in Two Population-Based Cohorts.

ABSTRACT: OBJECTIVE:Alcohol use disorders are common conditions that have enormous social and economic consequences. Genome-wide association analyses were performed to identify genetic variants associated with a proxy measure of alcohol consumption and alcohol misuse and to explore the shared genetic basis between these measures and other substance use, psychiatric, and behavioral traits. METHOD:This study used quantitative measures from the Alcohol Use Disorders Identification Test (AUDIT) from two population-based cohorts of European ancestry (UK Biobank [N=121,604] and 23andMe [N=20,328]) and performed a genome-wide association study (GWAS) meta-analysis. Two additional GWAS analyses were performed, a GWAS for AUDIT scores on items 1-3, which focus on consumption (AUDIT-C), and for scores on items 4-10, which focus on the problematic consequences of drinking (AUDIT-P). RESULTS:The GWAS meta-analysis of AUDIT total score identified 10 associated risk loci. Novel associations localized to genes including JCAD and SLC39A13; this study also replicated previously identified signals in the genes ADH1B, ADH1C, KLB, and GCKR. The dimensions of AUDIT showed positive genetic correlations with alcohol consumption (rg=0.76-0.92) and DSM-IV alcohol dependence (rg=0.33-0.63). AUDIT-P and AUDIT-C scores showed significantly different patterns of association across a number of traits, including psychiatric disorders. AUDIT-P score was significantly positively genetically correlated with schizophrenia (rg=0.22), major depressive disorder (rg=0.26), and attention deficit hyperactivity disorder (rg=0.23), whereas AUDIT-C score was significantly negatively genetically correlated with major depressive disorder (rg=-0.24) and ADHD (rg=-0.10). This study also used the AUDIT data in the UK Biobank to identify thresholds for dichotomizing AUDIT total score that optimize genetic correlations with DSM-IV alcohol dependence. Coding individuals with AUDIT total scores ?4 as control subjects and those with scores ?12 as case subjects produced a significant high genetic correlation with DSM-IV alcohol dependence (rg=0.82) while retaining most subjects. CONCLUSIONS:AUDIT scores ascertained in population-based cohorts can be used to explore the genetic basis of both alcohol consumption and alcohol use disorders.

SUBMITTER: Sanchez-Roige S

PROVIDER: S-EPMC6365681 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Genome-Wide Association Study Meta-Analysis of the Alcohol Use Disorders Identification Test (AUDIT) in Two Population-Based Cohorts.

Sanchez-Roige Sandra S Palmer Abraham A AA Fontanillas Pierre P Elson Sarah L SL Adams Mark J MJ Howard David M DM Edenberg Howard J HJ Davies Gail G Crist Richard C RC Deary Ian J IJ McIntosh Andrew M AM Clarke Toni-Kim TK

The American journal of psychiatry 20181019 2

<h4>Objective</h4>Alcohol use disorders are common conditions that have enormous social and economic consequences. Genome-wide association analyses were performed to identify genetic variants associated with a proxy measure of alcohol consumption and alcohol misuse and to explore the shared genetic basis between these measures and other substance use, psychiatric, and behavioral traits.<h4>Method</h4>This study used quantitative measures from the Alcohol Use Disorders Identification Test (AUDIT) ...[more]

PMID: 30336701

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Project description:ObjectiveGenome-wide association studies (GWASs) of the Alcohol Use Disorders Identification Test (AUDIT), a 10-item screen for alcohol use disorder (AUD), have elucidated novel loci for alcohol consumption and misuse. However, these studies also revealed that GWASs can be influenced by numerous biases (e.g., measurement error, selection bias), which may have led to inconsistent genetic correlations between alcohol involvement and AUD, as well as paradoxically negative genetic correlations between alcohol involvement and psychiatric disorders and/or medical conditions. The authors used genomic structural equation modeling to elucidate the genetics of alcohol consumption and problematic consequences of alcohol use as measured by AUDIT.MethodsTo explore these unexpected differences in genetic correlations, the authors conducted the first item-level and the largest GWAS of AUDIT items (N=160,824) and applied a multivariate framework to mitigate previous biases.ResultsThe authors identified novel patterns of similarity (and dissimilarity) among the AUDIT items and found evidence of a correlated two-factor structure at the genetic level ("consumption" and "problems," rg=0.80). Moreover, by applying empirically derived weights to each of the AUDIT items, the authors constructed an aggregate measure of alcohol consumption that was strongly associated with alcohol dependence (rg=0.67), moderately associated with several other psychiatric disorders, and no longer positively associated with health and positive socioeconomic outcomes. Lastly, by conducting polygenic analyses in three independent cohorts that differed in their ascertainment and prevalence of AUD, the authors identified novel genetic associations between alcohol consumption, alcohol misuse, and health.ConclusionsThis work further emphasizes the value of AUDIT for both clinical and genetic studies of AUD and the importance of using multivariate methods to study genetic associations that are more closely related to AUD.

Project description:BackgroundValidated tools for assessing alcohol use among young people in low-income countries are needed to estimate prevalence and evaluate alcohol-reduction interventions. We validated Alcohol Use Disorders Identification Test (AUDIT) against Timeline Follow Back (TLFB), Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and phosphatidylethanol (PEth); and the 30-day-AUDIT against the 12-months-AUDIT among young Ugandans.MethodsIn 2018, we collected retrospective data on 30-day and 12-month AUDIT, TLFB and DSM-5 in a cross-sectional study of 15-24?year old residents of Ugandan fishing communities. AUDIT was administered by Audio Computer Assisted Self-Interviewing (ACASI) and DSM-5 and TLFB by psychiatric nurses. We determined PEth16:0/18:1 levels from dried blood spots using liquid chromatography tandem-mass spectrometry (heavy usage, ?210?ng/mL) and calculated sensitivity and specificity of AUDIT against the other measures.ResultsAmong 1281 participants (52.7% male, mean age 20?years), half (n?=?659; 51.4%) reported ever drinking alcohol, 19.4% had 12-month-AUDIT???8 (21.5% men; 17.0% women), and 24.2% had 30-day-AUDIT???8 (29.0% men; 18.9% women). Twenty percent of participants had detectable PEth with 55 (4.3%) classified as heavy drinkers; 50.7% reported???2 symptoms on DSM-5 and 6.3% reported binge drinking in the previous month based on TLFB (8.9% men, 3.5% women). The 30-day-AUDIT???8 had sensitivity 86.7%, 95%CI: 81.8%-90.7% and specificity 90.9%, 95%CI:89.0%-92.6% versus 12-month-AUDIT???8. Both 30-day and 12-month-AUDIT???8 were sensitive and specific markers of heavy drinking by PEth (12-month-AUDIT sensitivity?=?80.0%; 95%CI:67.0%-89.6%; specificity?=?83.3%; 95%CI:81.1%-85.3%). The 30-day-AUDIT was a sensitive and specific marker of binge drinking based on TLFB (sensitivity?=?82.7%; 95%CI:72.7%-90.2%, specificity?=?79.8%; 95%CI:77.4%-82.1%); 12-month-AUDIT had lower sensitivity. Both 30-day and 12-month AUDIT???8 were highly specific but insensitive markers of having DSM-5???2 symptoms.ConclusionAmong young people in Uganda, ACASI-administered 30-day and 12-month-AUDIT have good diagnostic properties compared to PEth, DSM-5 and TLFB. Self-reported AUDIT provides a quick and valid means of assessing alcohol misuse in these communities.

Project description:Genetic markers of the endocannabinoid system have been linked to a variety of addiction-related behaviors that extend beyond cannabis use. In the current study we investigate the relationship between endocannabinoid (eCB) genetic markers and alcohol use disorder (AUD) in European adolescents (14-18 years old) followed in the IMAGEN study (n = 2,051) and explore replication in a cohort of North American adolescents from Canadian Saguenay Youth Study (SYS) (n = 772). Case-control status is represented by a score of more than 7 on the Alcohol Use Disorder Identification Test (AUDIT). First a set-based test method was used to examine if a relationship between the eCB system and AUDIT case/control status exists at the gene level. Using only SNPs that are both independent and significantly associated to case-control status, we perform Fisher's exact test to determine SNP level odds ratios in relation to case-control status and then perform logistic regressions as post-hoc analysis, while considering various covariates. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the most robust SNP×SNP interaction of the five eCB genes with positive AUDIT screen. While no gene-sets were significantly associated to AUDIT scores after correction for multiple tests, in the case/control analysis, 7 SNPs were significantly associated with AUDIT scores of > 7 (p < 0.05; OR<1). Two SNPs remain significant after correction by false discovery rate (FDR): rs9343525 in CNR1 (pcorrected =0.042, OR = 0.73) and rs507961 in MGLL (pcorrected = 0.043, OR = 0.78). Logistic regression showed that both rs9353525 (CNR1) and rs507961 (MGLL) remained significantly associated with positive AUDIT screens (p < 0.01; OR < 1) after correction for multiple covariables and interaction of covariable × SNP. This result was not replicated in the SYS cohort. The GMDR model revealed a significant three-SNP interaction (p = 0.006) involving rs484061 (MGLL), rs4963307 (DAGLA), and rs7766029 (CNR1) predicted case-control status, after correcting for multiple covariables in the IMAGEN sample. A binomial logistic regression of the combination of these three SNPs by phenotype in the SYS cohort showed a result in the same direction as seen in the IMAGEN cohort (BETA = 0.501, p = 0.06). While preliminary, the present study suggests that the eCB system may play a role in the development of AUD in adolescents.

Project description:Several psychometrically sound measures of alcohol use have been developed to assess drinking. The Alcohol Use Disorders Identification Test (AUDIT) and its shorter counterpart the AUDIT-C, which contains the first 3 AUDIT questions, were developed by the World Health Organization and have become the preferred brief measures for screening and evaluating problem severity. This study compared the first 3 questions on the AUDIT with another psychometrically sound brief measure of alcohol use, the Quick Drinking Screen (QDS).Data were obtained from a randomized controlled trial of a mail-based intervention promoting self-change with 472 alcohol abusers (n = 280, no prior alcohol treatment; n = 192, prior alcohol treatment). Participants' retrospective self-reports of alcohol consumption were collected using the QDS and the 3 AUDIT-C questions and compared. Although both measures contain similar questions (2 quantity-frequency and 1 binge drinking), they differ in 2 important ways: (i) temporal interval over which data are collected, and (ii) formatting of response options (i.e., a continuous number vs. categorical).Intraclass correlations for drinking variables were moderate to moderately high. A repeated-measures MANOVA using treatment condition and gender as variables revealed significant differences in absolute values between the 2 drinking measures with the QDS showing greater consumption on almost all variables. Participants' numerical answers on the QDS were compared to their categorical answers to the similar alcohol use questions on the AUDIT-C. The comparison revealed that participants' answers on the AUDIT-C were associated with extreme variability compared to their QDS answers. This variability suggests the AUDIT-C would be unreliable as a quantitative measure of alcohol consumption.The differences between the 3 alcohol use questions on the AUDIT-C and the same questions on the QDS may reflect the imprecision of the AUDIT-C's drinking response categories. Results suggest that the QDS can be used to identify risky drinking and to provide a more informative characterization of a drinker's alcohol consumption than that provided by the AUDIT-C.

Dataset Information

Genome-Wide Association Study Meta-Analysis of the Alcohol Use Disorders Identification Test (AUDIT) in Two Population-Based Cohorts.

Publications

Genome-Wide Association Study Meta-Analysis of the Alcohol Use Disorders Identification Test (AUDIT) in Two Population-Based Cohorts.

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