Genome-wide association study of alcohol use disorder identification test (AUDIT) scores in 20 328 research participants of European ancestry.
paper
Cited
Public
- Authors
- Sanchez-Roige, Sandra; Fontanillas, Pierre; Elson, Sarah L; 23andMe Research Team; Gray, Joshua C; de Wit, Harriet; Davis, Lea K; MacKillop, James; Palmer, Abraham A
- Year
- 2019
- Journal
- Addiction biology
- PMID
- 29058377
- DOI
- 10.1111/adb.12574
- PMCID
- PMC6988186
Genetic factors contribute to the risk for developing alcohol use disorder (AUD). In collaboration with the genetics company 23andMe, Inc., we performed a genome-wide association study of the alcohol use disorder identification test (AUDIT), an instrument designed to screen for alcohol misuse over the past year. Our final sample consisted of 20 328 research participants of European ancestry (55.3% females; mean age = 53.8, SD = 16.1) who reported ever using alcohol. Our results showed that the 'chip-heritability' of AUDIT score, when treated as a continuous phenotype, was 12%. No loci reached genome-wide significance. The gene ADH1C, which has been previously implicated in AUD, was among our most significant associations (4.4 × 10 ; rs141973904). We also detected a suggestive association on chromosome 1 (2.1 × 10 ; rs182344113) near the gene KCNJ9, which has been implicated in mouse models of high ethanol drinking. Using linkage disequilibrium score regression, we identified positive genetic correlations between AUDIT score, high alcohol consumption and cigarette smoking. We also observed an unexpected positive genetic correlation between AUDIT and educational attainment and additional unexpected negative correlations with body mass index/obesity and attention-deficit/hyperactivity disorder. We conclude that conducting a genetic study using responses to an online questionnaire in a population not ascertained for AUD may represent a cost-effective strategy for elucidating aspects of the etiology of AUD.
Distribution of AUDIT scores (prior to log transformation).
Results of GWAS on AUDIT. (a) Manhattan plot of GWAS results indicating the strongest associations between the 22 autosomes, X chromosome, and AUDIT. Line denotes genome-wide significance (P < 5 × 10−8).
Genetic correlations between AUDIT and several traits measured in independent cohorts as described in the Supplementary Table 9: (a) neuropsychiatric, (b) smoking, (c) personality, (d) cognition, (e) anthropomorphic. * P < 0.05, ** P < 0.01, *** P < 0.0001.
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In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Central amygdala single-nucleus atlas reveals chromatin and gene transcription dynamics in human alcohol use disorder. | Lee CY et al. | — | 2026 | → |
| Exploring the genetic overlap between substance use disorder and educational attainment. | Cabana-Domínguez J et al. | — | 2026 | → |
| Genetic substructure in Latin American individuals reveals novel associations, mechanistic insights, and variable polygenic risk score transferability for alcohol traits | Montalvo-Ortiz J et al. | — | 2026 | — |
| Genome-wide association study of delay discounting identifies 11 loci and reveals transdiagnostic associations across mental and physical health. | Thorpe HHA et al. | — | 2026 | → |
| Large-scale behavioral characterization of oxycodone self-administration in heterogeneous stock rats reveals initial analgesic effects are associated with addiction-like behaviors. | Kallupi M et al. | — | 2026 | → |
| Chronic ethanol exposure in mice evokes pre- and postsynaptic deficits in GABAergic transmission in ventral tegmental area GABA neurons. | Mitten EH et al. | — | 2025 | → |
| GRIK1 genotype and effect of topiramate for alcohol use: a systematic review. | Kotake K et al. | — | 2025 | → |
| Parental Remission From Alcohol Use Disorder Shows Limited Protective Effects on Offspring Alcohol Outcomes. | McCutcheon VV et al. | — | 2025 | → |
| A critical review of ethanol effects on neuronal firing: A metabolic perspective. | Popova D et al. | — | 2024 | → |
| A high-resolution PheWAS approach to alcohol-related polygenic risk scores reveals mechanistic influences of alcohol reinforcing value and drinking motives. | Deng WQ et al. | — | 2024 | → |
| A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals. | Jennings MV et al. | — | 2024 | → |
| Human genetics and epigenetics of alcohol use disorder. | Zhou H et al. | — | 2024 | → |
| Introduction: Approved treatments for alcohol use disorder by regulatory agencies. | Camarini R et al. | — | 2024 | → |
| Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes. | Toikumo S et al. | — | 2024 | → |
| Alcohol Consumption and Alcohol Use Disorder: Exposing an Increasingly Shared Genetic Architecture. | White JD et al. | — | 2023 | → |
| Association of parental divorce, discord, and polygenic risk with children's alcohol initiation and lifetime risk for alcohol use disorder. | Kuo SI et al. | — | 2023 | → |
| Case-only exome variation analysis of severe alcohol dependence using a multivariate hierarchical gene clustering approach. | Gentry AE et al. | — | 2023 | → |
| Cohort profile: Genetic data in the German Socio-Economic Panel Innovation Sample (SOEP-G). | Koellinger PD et al. | — | 2023 | → |
| Differences in genetic correlations between posttraumatic stress disorder and alcohol-related problems phenotypes compared to alcohol consumption-related phenotypes. | Bountress KE et al. | — | 2023 | → |
| Genetic associations between alcohol phenotypes and life satisfaction: a genomic structural equation modelling approach. | Bountress KE et al. | — | 2023 | → |
| Genetic nurture effects for alcohol use disorder. | Thomas NS et al. | — | 2023 | → |
| Missingness adapted group informed clustered (MAGIC)-LASSO: a novel paradigm for phenotype prediction to improve power for genetic loci discovery. | Gentry AE et al. | — | 2023 | → |
| The effects of age on the severity of problem drinking: Mediating effects of positive alcohol expectancy and neural correlates. | Chaudhary S et al. | — | 2023 | → |
| Alcohol-Induced Oxidative Stress and the Role of Antioxidants in Alcohol Use Disorder: A Systematic Review. | Tsermpini EE et al. | — | 2022 | → |
| Alcohol use and alcohol use disorder differ in their genetic relationships with PTSD: A genomic structural equation modelling approach. | Bountress KE et al. | — | 2022 | → |
| A Systematic Review of Genetic Polymorphisms Associated with Bipolar Disorder Comorbid to Substance Abuse. | de Marco A et al. | — | 2022 | → |
| Common and distinguishing genetic factors for substance use behavior and disorder: an integrated analysis of genomic and transcriptomic studies from both human and animal studies. | Chang XW et al. | — | 2022 | → |
| FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit. | Flippo KH et al. | — | 2022 | → |
| Genome-wide association mapping of ethanol sensitivity in the Diversity Outbred mouse population. | Parker CC et al. | — | 2022 | → |
| Genome-Wide Association Study on Three Behaviors Tested in an Open Field in Heterogeneous Stock Rats Identifies Multiple Loci Implicated in Psychiatric Disorders. | Gunturkun MH et al. | — | 2022 | → |
| Genome-wide meta-analysis of alcohol use disorder in East Asians. | Zhou H et al. | — | 2022 | → |
| Hazardous drinking and alcohol use disorders. | MacKillop J et al. | — | 2022 | → |
| Substance use and common contributors to morbidity: A genetics perspective. | Sanchez-Roige S et al. | — | 2022 | → |
| The role of adolescent social relationships in promoting alcohol resistance: Interrupting the intergenerational transmission of alcohol misuse. | Stephenson M et al. | — | 2022 | → |
| Alcohol use disorders and ADHD. | Luderer M et al. | — | 2021 | → |
| Dimensional Phenotypes in Psychiatric Genetics: Lessons from Genome-Wide Association Studies of Alcohol Use Phenotypes. | Mallard TT et al. | — | 2021 | → |
| Do gene expression findings from mouse models of cocaine use recapitulate human cocaine use disorder in reward circuitry? | Huggett SB et al. | — | 2021 | → |
| Genetic and shared couple environmental contributions to smoking and alcohol use in the UK population. | Clarke TK et al. | — | 2021 | → |
| Genetics of substance use disorders: a review. | Deak JD et al. | — | 2021 | → |
| Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes. | Xue A et al. | — | 2021 | → |
| <i>LRRK2</i> Gene Variants Associated With a Higher Risk for Alcohol Dependence in Multiethnic Populations. | Oliveira PRS et al. | — | 2021 | → |
| Integration of evidence across human and model organism studies: A meeting report. | Palmer RHC et al. | — | 2021 | → |
| Multi-omics integration analysis identifies novel genes for alcoholism with potential overlap with neurodegenerative diseases. | Kapoor M et al. | — | 2021 | → |
| Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples. | Johnson EC et al. | — | 2021 | → |
| Resource profile and user guide of the Polygenic Index Repository. | Becker J et al. | — | 2021 | → |
| The Cocaine and Oxycodone Biobanks, Two Repositories from Genetically Diverse and Behaviorally Characterized Rats for the Study of Addiction. | Carrette LLG et al. | — | 2021 | → |
| The impact of removing former drinkers from genome-wide association studies of AUDIT-C. | Dao C et al. | — | 2021 | → |
| Adolescent risk and protective factors predicting triple trajectories of substance use from adolescence into adulthood. | Lee JY et al. | — | 2020 | → |
| Alcohol and drug use disorders in adult attention-deficit/hyperactivity disorder: Prevalence and associations with attention-deficit/hyperactivity disorder symptom severity and emotional dysregulation. | Anker E et al. | — | 2020 | → |
| Alcohol Sensitivity as an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility between Rodents and Humans. | Parker CC et al. | — | 2020 | → |
| Differentiating Types of Self-Reported Alcohol Abstinence. | Gordon KS et al. | — | 2020 | → |
| Epigenetic changes on rat chromosome 4 contribute to disparate alcohol drinking behavior in alcohol-preferring and -nonpreferring rats. | Spence JP et al. | — | 2020 | → |
| Genetic architecture of cardiometabolic risks in people living with HIV. | Cheng H et al. | — | 2020 | → |
| On the path towards personalized medicine: Implications of pharmacogenetic studies of alcohol use disorder medications. | Nieto SJ et al. | — | 2020 | → |
| Recent Efforts to Dissect the Genetic Basis of Alcohol Use and Abuse. | Sanchez-Roige S et al. | — | 2020 | → |
| Translational Molecular Approaches in Substance Abuse Research. | Fulton SL et al. | — | 2020 | → |
| Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood. | Meyers JL et al. | — | 2019 | → |
| Beyond genome-wide significance: integrative approaches to the interpretation and extension of GWAS findings for alcohol use disorder. | Salvatore JE et al. | — | 2019 | → |
| Genetic determinants of beverage consumption: Implications for nutrition and health. | Cornelis MC | — | 2019 | → |
| Genetics of alcohol use disorder: a review. | Deak JD et al. | — | 2019 | → |
| Genome-Wide Association Studies of Impulsive Personality Traits (BIS-11 and UPPS-P) and Drug Experimentation in up to 22,861 Adult Research Participants Identify Loci in the <i>CACNA1I</i> and <i>CADM2</i> genes. | Sanchez-Roige S et al. | — | 2019 | → |
| Genome-Wide Association Study Meta-Analysis of the Alcohol Use Disorders Identification Test (AUDIT) in Two Population-Based Cohorts. | Sanchez-Roige S et al. | — | 2019 | → |
| Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. | Kranzler HR et al. | — | 2019 | → |
| Genome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci. | Gelernter J et al. | — | 2019 | → |
| The Genetic Relationship Between Alcohol Consumption and Aspects of Problem Drinking in an Ascertained Sample. | Johnson EC et al. | — | 2019 | → |
| Using DNA methylation to validate an electronic medical record phenotype for smoking. | McGinnis KA et al. | — | 2019 | → |
| Validation and characterisation of a DNA methylation alcohol biomarker across the life course. | Yousefi PD et al. | — | 2019 | → |
| Alcohol Dehydrogenases, Aldehyde Dehydrogenases, and Alcohol Use Disorders: A Critical Review. | Edenberg HJ et al. | — | 2018 | → |
| AUDIT-C and ICD codes as phenotypes for harmful alcohol use: association with ADH1B polymorphisms in two US populations. | Justice AC et al. | — | 2018 | → |
| Conflict-related medial frontal theta as an endophenotype for alcohol use disorder. | Harper J et al. | — | 2018 | → |
| Genetics of Alcohol Use Disorder: A Role for Induced Pluripotent Stem Cells? | Prytkova I et al. | — | 2018 | → |
| Human Genetics of Addiction: New Insights and Future Directions. | Hancock DB et al. | — | 2018 | → |
| Meta-Analysis of Genetic Influences on Initial Alcohol Sensitivity. | Edwards AC et al. | — | 2018 | → |
| Polygenic Risk Score Prediction of Alcohol Dependence Symptoms Across Population-Based and Clinically Ascertained Samples. | Savage JE et al. | — | 2018 | → |
| Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders. | Walters RK et al. | — | 2018 | → |