Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits.

paper Primary Public

Authors: Zhou, Hang; Sealock, Julia M; Sanchez-Roige, Sandra; Clarke, Toni-Kim; Levey, Daniel F; Cheng, Zhongshan; Li, Boyang; Polimanti, Renato; Kember, Rachel L; Smith, Rachel Vickers; Thygesen, Johan H; Morgan, Marsha Y; Atkinson, Stephen R; Thursz, Mark R; Nyegaard, Mette; Mattheisen, Manuel; Børglum, Anders D; Johnson, Emma C; Justice, Amy C; Palmer, Abraham A; McQuillin, Andrew; Davis, Lea K; Edenberg, Howard J; Agrawal, Arpana; Kranzler, Henry R; Gelernter, Joel
Year: 2020
Journal: Nature neuroscience
PMID: 32451486
DOI: 10.1038/s41593-020-0643-5
PMCID: PMC7485556

Figure 1.

Overview of the analysis.The four datasets that were meta-analyzed as the discovery sample for problematic alcohol use (PAU) included MVP phase1, MVP phase2, PGC, and UK Biobank (UKB). MVP phase1 and phase2 were meta-analyzed, and the result was used to test the genetic correlation with PGC alcohol dependence. An intermediary meta-analysis (AUD meta) combining MVP phase1, phase2, and PGC was then conducted to measure the genetic correlation with UKB AUDIT-P. Due to the sample overlap between UKB and GSCAN, we used the AUD (intermediary) meta-analysis for Mendelian Randomization (MR) analysis rather than the PAU (i.e., from the final) meta-analysis. MTAG, which used the summary data from PAU and DrnkWk (drinks per week) in GSCAN (without 23andMe samples, as those data were not available) as input to increase the power for each trait without introducing bias from sample overlap, returned summary results for PAU and DrnkWk separately.

Figure 2.

Association results for AUD and PAU meta-analyses.a. Manhattan and QQ plots for AUD (MVP+PGC), ncase=57,564, ncontrol=256,395, neffective=179,185; b. Manhattan and QQ plots for PAU, n=435,563, neffective=300,789. Effective sample size weighted meta-analyses were performed using METAL. Red lines indicate GWS after correction for multiple testing (p < 5×10–8).

Figure 3.

Estimated SNP-based h2.h2 results for single datasets or meta-analysis between datasets, from published studies or analyzed here. MVP is the phase1-phase2 MVP metaanalysis, PAU is the discovery meta-analysis. Effective sample sizes (nE) were used in LDSC. Center values are the estimated h2 and error bars indicate 95% confidence intervals.

Figure 4.

Genetic correlations with published traits.LDSC was applied to test genetic correlation between PAU and 715 traits. Of 228 published traits, 26 were genetically correlated with PAU after Bonferroni correction (p < 6.99×10−5). MDD, major depressive disorder; ADHD, attention deficit hyperactivity disorder. Center values are the estimated genetic correlation and error bars indicate 95% confidence intervals.

Figure 5.

Phenome-Wide associations with PAU PRS in BioVU.Polygenic score for PAU was calculated in 67,588 participants in BioVU (Vanderbilt University Medical Center’s biobank) using PRS-CS. 1,372 phenotypes were tested and Bonferroni correction (p < 3.64×10−5) was applied.

#	Section	Preview
0	Introduction	Alcohol use and alcohol use disorder (AUD) are leading causes of death and disability worldwide [1].…
1	Introduction	Beta Polypeptide), ADH1C (Alcohol Dehydrogenase 1C (class I), Gamma Polypeptide), ALDH2 (Aldehyde…
2	Results	Figure 1 provides an overview of the meta-analysis of the 4 major datasets. The first is the GWAS of…
3	Results	The genetic correlation (rg) between MVP phase1 AUD and PGC AD was 0.965 (se = 0.15, p = 1.21 ×…
4	Results — Association results for PAU	Of 42 lead variants (mapping to 27 loci, Figure 2b, and Supplementary Table 3) that were genome-wide…
5	Results — Association results for PAU	Adaptor 6A), and FUT2 (Fucosyltransferase 2). A novel rare ADH1B variant, rs75967634 (p = 1.07 ×…
6	Results — Association results for PAU	Moderate genetic correlation between AUD and alcohol consumption and pervasive pleiotropic effects…
7	Results — Association results for PAU	Gene-based association analysis identified 66 genes that were associated with PAU at GWS (p < 2.64…
8	Results — Association results for PAU	Examination of the 66 associated genes for known drug-gene interactions through the Drug Gene…
9	Results — SNP-based h2 and partitioning heritability enrichment	We used LD Score Regression (LDSC) [12] to estimate SNP-based h2 in the different datasests and the…
10	Results — SNP-based h2 and partitioning heritability enrichment	Partitioning heritability enrichment analyses using LDSC [13, 14] showed the most significantly…
11	Results — Functional enrichments	MAGMA tissue expression analysis [17, 18] using GTEx showed significant enrichments in several brain…
12	Results — Genetic correlations with other traits	We estimated the genetic correlations between PAU and 715 publicly available sets of GWAS summary…
13	Results — Genetic correlations with other traits	genetic correlation with PAU, extending the evidence for a shared genetic contribution to MDD and…
14	Results — Transcriptomic analyses	We used S-PrediXcan [23] to predict gene expression and the mediating effects of variation on gene…
15	Results — Transcriptomic analyses	Although the sample size for tissues used for eQTL analysis limits our ability to detect…
16	Results — PAU PRS for phenome-wide associations	We calculated PRS for PAU in 67,589 individuals of European descent from the Vanderbilt University…
17	Results — PAU PRS with AD in independent samples	We tested the association between PAU PRS and alcohol dependence in 3 independent samples: the…
18	Results — Mendelian Randomization	We tested the bi-directional causal effects between other traits and AUD (MVP+PGC), rather than PAU;…
19	Results — Mendelian Randomization	risk, and the estimate was robust after correction for horizontal pleiotropy. The “worry”…

Name	Type
1000 Genomes Project	cohort
1000 Genomes Project Phase 3 European sample local	cohort
23andMe	cohort
27 cohorts local	cohort
715 traits local	phenotype
absence of mental illness and harmful substance use local	phenotype
ADH1A	gene
ADH1B	gene
ADH1C	gene
ADH4	gene
ADH5	gene
ADH7	gene
ADH gene cluster	gene
ADH gene locus local	gene
adipose tissue	phenotype
adrenal local	anatomy
Affymetrix Biobank Array local	drug
African American	cohort
alcohol	phenotype
alcohol dependence	phenotype
alcoholic liver disease	phenotype
alcoholism	phenotype
alcohol-related phenotypes	phenotype
Alcohol Use	phenotype
Alcohol Use Disorder	phenotype
alcohol use disorders	phenotype
ALDH2	gene
Alzheimer's disease	phenotype
ARID4A	gene
Asian	cohort
AUD	phenotype
AUDIT	phenotype
AUDIT-C	phenotype
AUDIT-P	phenotype
AUD (MVP+PGC) local	phenotype
AUD PRS	drug
Bdnf	gene
BioVU	cohort
brain	anatomy
brain germinal matrix local	anatomy
C14orf2 local	gene
C1QTNF4 local	gene
Cadm2	gene
cardiovascular disease	phenotype
central nervous system	anatomy
cerebellum	anatomy
cognition	phenotype
CognitivePerformance local	phenotype
cognitive traits	phenotype
common SNPs (MAF > 0.05) local	variant
conditionally independent variant local	variant
conserved regions local	drug
conserved regions with 500bp extended local	drug
cortex	anatomy
CRHR1	gene
CYP2A6	gene
CYP2A6 activity local	phenotype
DGN	anatomy
DHS	drug
DPIM study AD arm local	cohort
Dpp6	gene
DRD2	gene
drinks per week	phenotype
drugs	drug
DSM-IV alcohol dependence	phenotype
Eagle2	drug
educational attainment	phenotype
ethanol consumption	phenotype
ethanol metabolic processes local	phenotype
European ancestry	cohort
European ancestry (EA) subjects local	cohort
European population	cohort
European population (EUR) local	cohort
Europeans	cohort
ever smoked regularly local	phenotype
EverSmokedRegularly local	phenotype
F10.2 local	phenotype
FastPCA	drug
fetal brain	anatomy
fetal DHS local	drug
FTO	gene
FUT2	gene
gastrointestinal local	anatomy
GCKR	gene
gene-based associations local	gene
GeneralRiskTolerance local	phenotype
GSCAN	cohort
GTEx	cohort
H3K27ac	drug
H3K36me3	drug
H3K3me3 local	drug
H3K4me1	drug
H3K4me3	drug
H3K9ac	drug
Haplotype Reference Consortium panel local	drug
HapMap3	cohort
heart	anatomy
heritability enrichment local	phenotype
histone mark H3K4me1 local	drug
HRC panel local	drug
Illumina	drug
Illumina Human Core Exome Array local	drug
immune and hematopoietic local	anatomy
independent variant local	variant
index variant	variant
insomnia	phenotype
iPSYCH	cohort
iPSYCH group local	cohort
Klb	gene
LD Hub	cohort
lifetime cannabis use	phenotype
liver	anatomy
major depressive disorder	phenotype
Million Veteran Program	cohort
minimac3	drug
mood disorders	phenotype
MVP	cohort
MVP meta-analysis	cohort
MVP+PGC local	cohort
MVP phase1 local	cohort
MVP phase1 AUD local	phenotype
MVP phase1 sample local	cohort
MVP phase2 local	cohort
MVP phase2 dataset local	cohort
newborn bloodspots local	cohort
novel variant	cohort
number of sexual partners	phenotype
NumberSexualPartners local	phenotype
pancreas	anatomy
parents’ age at death local	phenotype
PAU	phenotype
PAU liability local	phenotype
PAU polygenic score local	drug
PAU PRS	phenotype
Pde4b	gene
PGC	cohort
PGC AD	cohort
PGC AD local	phenotype
PGC AD GWAS local	cohort
Phase1 local	cohort
Phase2 local	cohort
phase2 EAs local	cohort
phs001672.v3.p1 local	cohort
Plink1.9 local	drug
population registry data local	cohort
problematic alcohol use	phenotype
PRS of AUD local	drug
Psych Array local	drug
psychiatric disorders	phenotype
Psychiatric Genomics Consortium	cohort
psychiatric traits	phenotype
published traits local	phenotype
Respiratory conditions local	phenotype
risk allele	cohort
risk loci	cohort
risk-taking behavior	phenotype
Roadmap Epigenomics consortium	cohort
rs10717830 local	variant
rs12296477 local	variant
rs1229984	variant
rs13125415 local	variant
rs1402398 local	variant
rs1612735 local	variant
rs1783835 local	variant
rs2066702	variant
rs2533200 local	variant
rs2683616 local	variant
rs492602 local	variant
rs61974485 local	variant
rs62250713 local	variant
rs6421482 local	variant
rs72768626 local	variant
rs75967634	variant
Sanger Imputation server local	drug
schizophrenia	phenotype
SIX3	gene
SLC39A13	gene
SLC39A8	gene
smoking phenotypes	phenotype
S-MultiXcan	drug
SNP	cohort
STOPAH trial local	cohort
study cohort	cohort
substance use	phenotype
SYNGAP1	gene
THSD7B	gene
thyroid local	anatomy
TMX2	gene
TNRC6A local	gene
tobacco dependence	phenotype
TSS local	drug
UCL Core Exome Array local	cohort
UCL Psych Array local	cohort
UKB	cohort
UKB AUDIT-P local	phenotype
UK Biobank	cohort
UK Household Longitudinal Study local	cohort
UK subjects local	cohort
U.S. Department of Veterans Affairs	cohort
variant	cohort
VRK2	gene
weak enhancers local	drug
White-British local	cohort
WorryNeuroticism local	phenotype
worry sub-cluster local	phenotype
Worry sub-cluster of neuroticism local	phenotype

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Genetic diversity fuels gene discovery for tobacco and alcohol use.	2022	36477530
Multi-omics signatures of alcohol use disorder in the dorsal and ventral striatum.	2022	35523767
Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality.	2021	33431810
Multi-omics integration analysis identifies novel genes for alcoholism with potential overlap with neurodegenerative diseases.	2021	34417470

External

Title	Authors	Journal	Year	Link
Advancing substance use disorder biology by studying underlying gene x environment interactions.	Sidamon-Eristoff AE et al.	—	2026	→
A large-scale DNA methylation study of alcohol use identified robust associations and cell-type specific insights.	Clark SL et al.	—	2026	→
Alcohol use disorder-associated gene FNDC4 alters glutamatergic and GABAergic neurogenesis in neural organoids.	Zhu X et al.	—	2026	→
Bulk and single-cell transcriptomic brain data identify overlapping processes and cell-types with human AUD and mammalian models of alcohol use.	Huggett SB et al.	—	2026	→
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	→
Gastrointestinal traits, common inflammatory disorders, gallstones, and biliary tract cancer: A network Mendelian randomization study.	Bai Y et al.	—	2026	→
Genome-wide association studies of lifetime and frequency of cannabis use in 131,895 individuals.	Thorpe HHA et al.	—	2026	→
Genome-wide meta-analyses of cross substance use disorders in diverse populations.	Lai D 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	→
<i>BDNF</i> gene polymorphisms and substance use disorders: a systematic review.	Peregud D et al.	—	2026	→
Mapping the genetic landscape across 14 psychiatric disorders.	Grotzinger AD et al.	—	2026	→
Multimodal profiling of gray matter differences in alcohol use disorder: An integrated SDM-PSI meta-analysis with neuroimaging fusion study.	Long S et al.	—	2026	→
Multivariate genetic analyses of 2.2 million individuals reveal broad and substance-specific pathways of addiction risk.	Poore HE et al.	—	2026	→
Optimizing Control Definitions in Opioid Use Disorder Genetic Research Using Electronic Health Records	Niarchou M et al.	—	2026	→
The Contributions of Multiple Polygenic Scores in Predicting Liability for Major Depressive Disorder and Its Comorbidity with Alcohol Use Disorder.	Wells JL et al.	—	2026	→
The genetics of cannabis lifetime use.	Bright U et al.	—	2026	→
A Comprehensive 4-layered <i>In Silico</i> Pharmacogenomics Analysis of the Genetic Addiction Risk Severity (GARS) Test: Strong Genetic Evidence Supporting GARS as a Novel Personalized Pre-addiction Assessment Tool in the Opioid Crisis Era.	Sharafshah A et al.	—	2025	→
A contextual genomic perspective on physical activity and its relationship to health, well being and illness.	Galimberti M et al.	—	2025	→
Addiction Susceptibility: Genetic Factors, Personality Traits, and Epigenetic Interactions with the Gut Microbiome.	Borrego-Ruiz A et al.	—	2025	→
Addressing overfitting bias due to sample overlap in polygenic risk scoring.	Jeong S et al.	—	2025	→
Alcohol use disorder and body mass index show genetic pleiotropy and shared neural associations.	Malone SG et al.	—	2025	→
A multi-omics Mendelian randomization study identifies new therapeutic targets for alcohol use disorder and problem drinking.	Rosoff DB et al.	—	2025	→
Are Depressive and Anxiety Symptoms Differentially Associated with Alcohol Use Behaviors: Multivariate Behavioral Genetic Analyses.	Chen T et al.	—	2025	→
Assessing the association between ADH5 and ALDH1A1 genetic variants and substance use disorder risk in a Jordanian male population.	Al-Eitan L et al.	—	2025	→
Association Between GABRG2 and Self-Rating of the Effects of Alcohol in a French Young Adult Sample.	Moe JS et al.	—	2025	→
Clinical, Genomic, and Neurophysiological Correlates of Lifetime Suicide Attempts among Individuals with an Alcohol Use Disorder.	Barr PB et al.	—	2025	→
Differences and similarities between the genetic architecture of lifetime substance use across different substances.	Bright U et al.	—	2025	→
Dissecting the causal effects of smoking, alcohol consumption, and related DNA methylation markers on electrocardiographic indices.	Zheng Z et al.	—	2025	→
Externalizing as a common genetic influence for a broad spectrum of substance use and behavioral conditions: A developmental perspective from the Avon Longitudinal Study of Parents and Children.	Deng WQ et al.	—	2025	→
Functional Validation of Alcohol Dependence-Associated <i>FYN</i> Variants Using Gene Editing and Stem Cell Study Approaches.	Cakir B et al.	—	2025	→
Gene expression differences associated with alcohol use disorder in human brain.	Willis C et al.	—	2025	→
Genetic analysis of alcohol use disorder: GWAS of alcohol use disorders identification test (AUDIT) and polygenic risk scores in an east slavic population.	Trofimov M et al.	—	2025	→
Genetic associations between orexin genes and phenotypes related to behavioral regulation in humans, including substance use.	Aliev F et al.	—	2025	→
Genetic correlations of alcohol consumption and alcohol use disorder with sex hormone levels in females and males.	Waller TC et al.	—	2025	→
Genetic liability for anxiety and treatment response to the monoamine stabilizer OSU6162 in alcohol dependence: a retrospective secondary analysis.	Hong MG et al.	—	2025	→
Genetic mapping in collaborative cross mouse strains identifies loci that affect initial sensitivity to cocaine.	Schoenrock SA et al.	—	2025	→
Genetic overlap between treatment-resistant schizophrenia and smoking initiation	Koch E et al.	—	2025	—
Genetic risk for alcohol use disorder in relation to individual symptom criteria: Do polygenic indices provide unique information for understanding severity and heterogeneity?	Sarles YM et al.	—	2025	→
Genetic risk for trait aggression and alcohol use predict unique facets of alcohol-related aggression.	Spychala KM et al.	—	2025	→
Genome-wide analyses of variance in blood cell phenotypes provide new insights into complex trait biology and prediction.	Xiang R et al.	—	2025	→
Genome-Wide Association Studies of Delay Discounting and Impulsive Personality Traits in Children From the Adolescent Behavior and Cognitive Development Study.	Deng WQ et al.	—	2025	→
Genotype-by-sex interaction analyses for alcohol use disorder across biobanks.	Zhou H et al.	—	2025	→
GRIK1 genotype and effect of topiramate for alcohol use: a systematic review.	Kotake K et al.	—	2025	→
Identification of ethanol analgesia quantitative trait loci and candidate genes in BXD recombinant inbred mouse lines.	Rogers WD et al.	—	2025	→
Identification of potential therapeutic targets for problematic alcohol use using multi-omics data.	Lee DJ et al.	—	2025	→
Identification of risk variants and cross-disorder pleiotropy through multi-ancestry genome-wide analysis of alcohol use disorder.	Icick R et al.	—	2025	→
Integrated single-cell multiomic profiling of caudate nucleus suggests key mechanisms in alcohol use disorder.	Green NC et al.	—	2025	→
Investigating the Contribution of Coding Variants in Alcohol Use Disorder Using Whole-Exome Sequencing Across Ancestries.	Wang L et al.	—	2025	→
Longitudinal characterization of impulsivity phenotypes boosts signal for genomic correlates and heritability.	Deng WQ et al.	—	2025	→
Low Stability and Specificity of Polygenic Risk Scores for Major Psychiatric Disorders Limit Their Clinical Utility.	Mollon J et al.	—	2025	→
Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions.	Vattathil SM et al.	—	2025	→
Measures of General Intelligence and Risk for Alcohol Use Disorder.	Capusan AJ et al.	—	2025	→
Modeling Brain Gene Expression in Alcohol Use Disorder with Genetic Animal Models.	Hitzemann R et al.	—	2025	→
Molecular Effect of Variants in Serotonin Transporter Gene in Women with Alcohol Use Disorder.	Rychel M et al.	—	2025	→
Next-generation biomarkers for alcohol consumption and alcohol use disorder diagnosis, prognosis, and treatment: A critical review.	Clark SL et al.	—	2025	→
Overexpression of OTX2 in human neural cells links depression risk genes.	Feng Y et al.	—	2025	→
Parental Remission From Alcohol Use Disorder Shows Limited Protective Effects on Offspring Alcohol Outcomes.	McCutcheon VV et al.	—	2025	→
Precision medicine in substance use disorders: Integrating behavioral, environmental, and biological insights.	Guerrin CGJ et al.	—	2025	→
Reevaluating the brain disease model of addiction.	Blithikioti C et al.	—	2025	→
Sex differences in nucleus accumbens circuitry engaged with binge-like ethanol drinking.	Chan AE et al.	—	2025	→
Similarities and Differences in Genetics.	Liu W et al.	—	2025	→
The BioSUD Biobank as a genomic resource for substance use disorders in Italy.	Ribatti RM et al.	—	2025	→
The Dopamine System in Mediating Alcohol Effects in Humans.	Beck A et al.	—	2025	→
The moderation of genetic risk for ten major psychiatric and substance use disorders by the genetic aptitude for educational attainment.	Kendler KS et al.	—	2025	→
The role of personality traits and life stress in alcohol use disorder: Insights from NGF gene polymorphisms of Han Chinese population in Taiwan.	Kuo SC et al.	—	2025	→
Understanding the alcohol harm paradox: A multivariable mendelian randomization approach.	Sawyer G et al.	—	2025	→
Whole Genome Sequencing of Pedigrees With High Density of Substance Use and Psychiatric Disorders: A Meeting Report.	Hill SY et al.	—	2025	→
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	→
Alcohol drinking, DNA methylation and psychiatric disorders: A multi-omics Mendelian randomization study to investigate causal pathways.	Shi X et al.	—	2024	→
Alcohol Exposure and Disease Associations: A Mendelian Randomization and Meta-Analysis on Weekly Consumption and Problematic Drinking.	Li M et al.	—	2024	→
Alcohol milestones and internalizing, externalizing, and executive function: longitudinal and polygenic score associations.	Paul SE 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	→
Are Psychiatric Disorders Brain Diseases?-A New Look at an Old Question.	Kendler KS	—	2024	→
Associations between alcohol use disorder polygenic score and remission in participants from high-risk families and the Indiana Biobank.	Lai D et al.	—	2024	→
Cell-type brain-region specific changes in prefrontal cortex of a mouse model of alcohol dependence.	Salem NA et al.	—	2024	→
Clinical associations with treatment resistance in depression: An electronic health record study.	Coombes BJ et al.	—	2024	→
Coordination among frequent genetic variants imparts substance use susceptibility and pathogenesis.	Veerappa A et al.	—	2024	→
Disentangling differing relationships between internalizing disorders and alcohol use.	Brasher MS et al.	—	2024	→
Examining the association between the FTO gene and neuroticism reveals indirect effects on subjective well-being and problematic alcohol use.	Cai W et al.	—	2024	→
Exploring the Causal Relationship Between Migraine and Insomnia Through Bidirectional Two-Sample Mendelian Randomization: A Bidirectional Causal Relationship.	Ouyang D et al.	—	2024	→
Generalized genetic liability to substance use disorders.	Miller AP et al.	—	2024	→
Genetic and non-genetic predictors of risk for opioid dependence.	Na PJ et al.	—	2024	→
Genetic architecture of the structural connectome.	Wainberg M et al.	—	2024	→
Genetic factors associated with suicidal behaviors and alcohol use disorders in an American Indian population.	Peng Q et al.	—	2024	→
Genetic Heterogeneity Across Dimensions of Alcohol Use Behaviors.	Savage JE et al.	—	2024	→
Genetic influences on alcohol sensitivity: A critical review.	Yeung EW et al.	—	2024	→
Genetics of gambling disorder and related phenotypes: The potential uses of polygenic and multifactorial risk models to enable early detection and improve clinical outcomes.	Warrier V et al.	—	2024	→
Human genetics and epigenetics of alcohol use disorder.	Zhou H et al.	—	2024	→
Identification of novel genetic loci and candidate genes for progressive ethanol consumption in diversity outbred mice.	Mignogna KM et al.	—	2024	→
Is low-level alcohol consumption really health-protective? A critical review of approaches to promote causal inference and recent applications.	Visontay R et al.	—	2024	→
Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies.	Li Y et al.	—	2024	→
Machine Learning of Functional Connectivity to Biotype Alcohol and Nicotine Use Disorders.	Zhu T et al.	—	2024	→
Major Psychiatric Disorders, Substance Use Behaviors, and Longevity.	Rosoff DB et al.	—	2024	→
Medical and genetic correlates of long-term buprenorphine treatment in the electronic health records.	Niarchou M et al.	—	2024	→
Mendelian randomization analyses reveal causal relationships between brain functional networks and risk of psychiatric disorders.	Mu C et al.	—	2024	→
Neurogenetic and multi-omic sources of overlap among sensation seeking, alcohol consumption, and alcohol use disorder.	Miller AP et al.	—	2024	→
Neuronal-specific methylome and hydroxymethylome analysis reveal significant loci associated with alcohol use disorder.	Andrade-Brito DE et al.	—	2024	→
Partitioning the Genomic Components of Behavioral Disinhibition and Substance Use (Disorder) Using Genomic Structural Equation Modeling.	Horwitz TB et al.	—	2024	→
Pleiotropy and genetically inferred causality linking multisite chronic pain to substance use disorders.	Koller D et al.	—	2024	→
Refining the scope of genetic influences on alcohol misuse through environmental stratification and gene-environment interaction.	Savage JE et al.	—	2024	→
Risk of severe mood and anxiety disorders in the adult children of parents with alcohol use disorder: a nationwide cohort study.	Kane K et al.	—	2024	→
The genetic landscape of substance use disorders.	Gerring ZF et al.	—	2024	→
The single-cell opioid responses in the context of HIV (SCORCH) consortium.	Ament SA et al.	—	2024	→
Unsupervised deep representation learning enables phenotype discovery for genetic association studies of brain imaging.	Patel K et al.	—	2024	→
Using a comprehensive atlas and predictive models to reveal the complexity and evolution of brain-active regulatory elements.	Pratt HE et al.	—	2024	→
Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR of FAIM2.	Littleton SH et al.	—	2024	→
What Are the Genetic Building Blocks of Alcohol-Related Behaviors?	Gelernter J et al.	—	2024	→
Whole exome sequencing analysis identifies genes for alcohol consumption.	Kang J et al.	—	2024	→
5. Collaborative Study on the Genetics of Alcoholism: Functional genomics.	Gameiro-Ros I et al.	—	2023	→
Adult alcohol drinking and emotional tone are mediated by neutral sphingomyelinase during development in males.	Kalinichenko LS et al.	—	2023	→
Alcohol Consumption and Alcohol Use Disorder: Exposing an Increasingly Shared Genetic Architecture.	White JD et al.	—	2023	→
Alcohol use and grey matter structure: Disentangling predispositional and causal contributions in human studies.	Baranger DAA et al.	—	2023	→
Alcohol use polygenic risk score, social support, and alcohol use among European American and African American adults.	Su J et al.	—	2023	→
A multivariate approach to understanding the genetic overlap between externalizing phenotypes and substance use disorders.	Poore HE et al.	—	2023	→
Analysis of the brain transcriptome for substance-associated genes: An update on large-scale genome-wide association studies.	Zhao Y 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	→
Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study.	Schaefer JD et al.	—	2023	→
Case-only exome variation analysis of severe alcohol dependence using a multivariate hierarchical gene clustering approach.	Gentry AE et al.	—	2023	→
Characterizing Alcohol Expectancies in the ABCD Study: Associations with Sociodemographic Factors, the Immediate Social Environment, and Genetic Propensities.	Johnson EC et al.	—	2023	→
COVID-19 pandemic stressors are associated with reported increases in frequency of drunkenness among individuals with a history of alcohol use disorder.	Meyers JL et al.	—	2023	→
Depression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses.	Als TD et al.	—	2023	→
Diagnostic Criteria for Identifying Individuals at High Risk of Progression From Mild or Moderate to Severe Alcohol Use Disorder.	Miller AP 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	→
Dimensional and transdiagnostic phenotypes in psychiatric genome-wide association studies.	Waszczuk MA et al.	—	2023	→
Dissecting the epigenomic differences between smoking and nicotine dependence in a veteran cohort.	Nagamatsu ST et al.	—	2023	→
Examining interactions between polygenic scores and interpersonal trauma exposure on alcohol consumption and use disorder in an ancestrally diverse college cohort.	Sheerin CM et al.	—	2023	→
Functional and molecular characterization of suicidality factors using phenotypic and genome-wide data.	Quintero Reis A et al.	—	2023	→
Functional Variation in the <i>FAAH</i> Gene Is Directly Associated with Subjective Well-Being and Indirectly Associated with Problematic Alcohol Use.	Bornscheuer L et al.	—	2023	→
Genetic architecture of ADHD and overlap with other psychiatric disorders and cognition-related phenotypes.	Ribasés M et al.	—	2023	→
Genetic associations between alcohol phenotypes and life satisfaction: a genomic structural equation modelling approach.	Bountress KE et al.	—	2023	→
Genetic predisposition to major depressive disorder differentially impacts alcohol consumption and high-risk drinking situations in men and women with alcohol use disorder.	Karpyak VM et al.	—	2023	→
Genetic Underpinnings of the Transition From Alcohol Consumption to Alcohol Use Disorder: Shared and Unique Genetic Architectures in a Cross-Ancestry Sample.	Kember RL et al.	—	2023	→
Genome- and transcriptome-wide splicing associations with alcohol use disorder.	Huggett SB et al.	—	2023	→
Genomic patterns linked to gray matter alterations underlying working memory deficits in adults and adolescents with attention-deficit/hyperactivity disorder.	Duan K et al.	—	2023	→
Identifying genetic loci and phenomic associations of substance use traits: A multi-trait analysis of GWAS (MTAG) study.	Xu H et al.	—	2023	→
Integrative Post-Genome-Wide Association Study Analyses Relevant to Psychiatric Disorders: Imputing Transcriptome and Proteome Signals.	Gedik H et al.	—	2023	→
Investigating genetically stratified subgroups to better understand the etiology of alcohol misuse.	Thijssen AB et al.	—	2023	→
Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder.	Johnson EC et al.	—	2023	→
Invited Expert Opinion- Bioinformatic and Limitation Directives to Help Adopt Genetic Addiction Risk Screening and Identify Preaddictive Reward Dysregulation: Required Analytic Evidence to Induce Dopamine Homeostatsis.	Blum K et al.	—	2023	→
Low Dopamine D2 Receptor Expression Drives Gene Networks Related to GABA, cAMP, Growth and Neuroinflammation in Striatal Indirect Pathway Neurons.	Guerri L et al.	—	2023	→
Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals.	Zhou H et al.	—	2023	→
Multi-omics cannot replace sample size in genome-wide association studies.	Baranger DAA et al.	—	2023	→
Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders.	Hatoum AS et al.	—	2023	→
Natural allelic variation modifies acute ethanol response phenotypes in wild strains of C. elegans.	van Wijk MH et al.	—	2023	→
Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample.	Kember RL et al.	—	2023	→
Positive personality traits moderate persistent high alcohol consumption, determined by polygenic risk in U.S. military veterans: results from a 10-year, population-based, observational cohort study.	Na P et al.	—	2023	→
RNA alternative splicing impacts the risk for alcohol use disorder.	Li R et al.	—	2023	→
Shared genetic and environmental etiology between substance use disorders and suicidal behavior.	Edwards AC et al.	—	2023	→
Smoking, alcohol consumption, and frailty: A Mendelian randomization study.	Lv J et al.	—	2023	→
The association between the <i>CCDC88A</i> gene polymorphism at rs1437396 and alcohol use disorder, with or without major depression disorder.	Bonea M et al.	—	2023	→
The Collaborative Study on the Genetics of Alcoholism: Overview.	Agrawal A et al.	—	2023	→
The Genetically Informed Neurobiology of Addiction (GINA) model.	Bogdan R et al.	—	2023	→
The Physiological and Pathological Role of Acyl-CoA Oxidation.	Szrok-Jurga S et al.	—	2023	→
The Stage-Based Model of Addiction-Using <i>Drosophila</i> to Investigate Alcohol and Psychostimulant Responses.	Cummins-Beebee PN et al.	—	2023	→
Usual dietary intake and change in DNA methylation over years: EWAS in KORA FF4 and KORA fit.	Hellbach F et al.	—	2023	→
Addictive behavior and incident gallstone disease: A dose-response meta-analysis and Mendelian randomization study.	Bai Y et al.	—	2022	→
A Genome-Wide Association Study Reveals a <i>BDNF</i>-Centered Molecular Network Associated with Alcohol Dependence and Related Clinical Measures.	Levchenko A et al.	—	2022	→
Alcohol and nicotine polygenic scores are associated with the development of alcohol and nicotine use problems from adolescence to young adulthood.	Deak JD et al.	—	2022	→
Alcohol consumption and telomere length: Mendelian randomization clarifies alcohol's effects.	Topiwala A et al.	—	2022	→
Alcohol consumption, blood DNA methylation and breast cancer: a Mendelian randomisation study.	Zhou X et al.	—	2022	→
Alcohol consumption, DNA methylation and colorectal cancer risk: Results from pooled cohort studies and Mendelian randomization analysis.	Zhou X 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	→
Alcohol Use and Use Disorder and Cancer Risk: Perspective on Causal Inference.	Zhou H et al.	—	2022	→
A Local Genetic Correlation Analysis Provides Biological Insights Into the Shared Genetic Architecture of Psychiatric and Substance Use Phenotypes.	Gerring ZF et al.	—	2022	→
An integrated framework for local genetic correlation analysis.	Werme J et al.	—	2022	→
Apremilast-induced increases in acute ethanol intoxication and decreases in ethanol drinking in mice involve PKA phosphorylation of GABA<sub>A</sub> β3 subunits.	Blednov YA et al.	—	2022	→
A scoping review and comparison of approaches for measuring genetic heterogeneity in psychiatric disorders.	Wang H et al.	—	2022	→
Associations between cognition and polygenic liability to substance involvement in middle childhood: Results from the ABCD study.	Paul SE et al.	—	2022	→
Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses.	Topiwala A et al.	—	2022	→
Associations of carotid intima media thickness with gene expression in whole blood and genetically predicted gene expression across 48 tissues.	Castaneda AB et al.	—	2022	→
A Systematic Review of Genetic Polymorphisms Associated with Bipolar Disorder Comorbid to Substance Abuse.	de Marco A et al.	—	2022	→
A three-factor model of common early onset psychiatric disorders: temperament, adversity, and dopamine.	Iqbal M et al.	—	2022	→
Chromatin architecture in addiction circuitry identifies risk genes and potential biological mechanisms underlying cigarette smoking and alcohol use traits.	Sey NYA et al.	—	2022	→
Clinical, environmental, and genetic risk factors for substance use disorders: characterizing combined effects across multiple cohorts.	Barr PB et al.	—	2022	→
CNest: A novel copy number association discovery method uncovers 862 new associations from 200,629 whole-exome sequence datasets in the UK Biobank.	Fitzgerald T et al.	—	2022	→
Comorbidity between mood and substance-related disorders: A systematic review and meta-analysis.	Saha S et al.	—	2022	→
Convergence of case-specific epigenetic alterations identify a confluence of genetic vulnerabilities tied to opioid overdose.	Corradin O et al.	—	2022	→
Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction.	Kember RL et al.	—	2022	→
Effects of genetic risk for alcohol dependence and onset of regular drinking on the progression to alcohol dependence: A polygenic risk score approach.	Yeung EW et al.	—	2022	→
Epigenetic Signatures of Smoking in Five Brain Regions.	Zillich L et al.	—	2022	→
Epigenome-wide association study of alcohol use disorder in five brain regions.	Zillich L et al.	—	2022	→
Evaluating risk for alcohol use disorder: Polygenic risk scores and family history.	Lai D et al.	—	2022	→
Gene-based polygenic risk scores analysis of alcohol use disorder in African Americans.	Lai D et al.	—	2022	→
Genes regulating levels of ω-3 long-chain polyunsaturated fatty acids are associated with alcohol use disorder and consumption, and broader externalizing behavior in humans.	Aliev F et al.	—	2022	→
Genetic Addiction Risk Severity Assessment Identifies Polymorphic Reward Genes as Antecedents to Reward Deficiency Syndrome (RDS) Hypodopaminergia's Effect on Addictive and Non-Addictive Behaviors in a Nuclear Family.	Dennen CA et al.	—	2022	→
Genetic and environmental etiology of drinking motives in college students.	Savage JE et al.	—	2022	→
Genetic diversity fuels gene discovery for tobacco and alcohol use.	Saunders GRB et al.	—	2022	→
Genetic liability for substance use associated with medical comorbidities in electronic health records of African- and European-ancestry individuals.	Hartwell EE et al.	—	2022	→
Genetic Variability of Incretin Receptors and Alcohol Dependence: A Pilot Study.	Tsermpini EE 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 in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci.	Deak JD et al.	—	2022	→
Genome-Wide Investigation of Maximum Habitual Alcohol Intake in US Veterans in Relation to Alcohol Consumption Traits and Alcohol Use Disorder.	Deak JD 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	→
Identifying and Reducing Bias in Genome-Wide Association Studies of Alcohol-Related Traits.	Kranzler HR et al.	—	2022	→
Integrating human brain proteomic data with genome-wide association study findings identifies novel brain proteins in substance use traits.	Toikumo S et al.	—	2022	→
Item-Level Genome-Wide Association Study of the Alcohol Use Disorders Identification Test in Three Population-Based Cohorts.	Mallard TT et al.	—	2022	→
Molecular genetics of cocaine use disorders in humans.	Fernàndez-Castillo N et al.	—	2022	→
Multi-omics signatures of alcohol use disorder in the dorsal and ventral striatum.	Zillich L et al.	—	2022	→
Novel digital approaches to the assessment of problematic opioid use.	Freda PJ et al.	—	2022	→
Pairwise genetic meta-analyses between schizophrenia and substance dependence phenotypes reveals novel association signals with pharmacological significance.	Greco LA et al.	—	2022	→
Parsing genetically influenced risk pathways: genetic loci impact problematic alcohol use via externalizing and specific risk.	Barr PB et al.	—	2022	→
Principal Component Analysis Reduces Collider Bias in Polygenic Score Effect Size Estimation.	Thomas NS et al.	—	2022	→
Reward Deficiency Syndrome (RDS) Surprisingly Is Evolutionary and Found Everywhere: Is It "Blowin' in the Wind"?	Blum K et al.	—	2022	→
RNA biomarkers for alcohol use disorder.	Ferguson LB et al.	—	2022	→
Shared mechanisms across the major psychiatric and neurodegenerative diseases.	Wingo TS et al.	—	2022	→
Statistical Validation of Risk Alleles in Genetic Addiction Risk Severity (GARS) Test: Early Identification of Risk for Alcohol Use Disorder (AUD) in 74,566 Case-Control Subjects.	Blum K et al.	—	2022	→
Strong and weak cross-inheritance of substance use disorders in a nationally representative sample.	Zhang H et al.	—	2022	→
Substance use and common contributors to morbidity: A genetics perspective.	Sanchez-Roige S et al.	—	2022	→
The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates.	Hatoum AS et al.	—	2022	→
The cannabinoid receptor-1 gene interacts with stressful life events to increase the risk for problematic alcohol use.	Bornscheuer L et al.	—	2022	→
Why haven't we solved the addiction crisis?	Blum K et al.	—	2022	→
Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant <i>ALDH2*2</i> Gene Allele.	Chen YC et al.	—	2021	→
Alcohol and cigarette smoking consumption as genetic proxies for alcohol misuse and nicotine dependence.	Sanchez-Roige S et al.	—	2021	→
Alcohol and the brain: from genes to circuits.	Egervari G et al.	—	2021	→
An integrative systems-based analysis of substance use: eQTL-informed gene-based tests, gene networks, and biological mechanisms.	Gerring ZF et al.	—	2021	→
Associations between Suicidal Thoughts and Behaviors and Genetic Liability for Cognitive Performance, Depression, and Risk-Taking in a High-Risk Sample.	Johnson EC et al.	—	2021	→
Biobank Scale Pharmacogenomics Informs the Genetic Underpinnings of Simvastatin Use.	Wendt FR et al.	—	2021	→
Brain structure and problematic alcohol use: a test of plausible causation using latent causal variable analysis.	Hatoum AS et al.	—	2021	→
Chronic Alcohol Use Induces Molecular Genetic Changes in the Dorsomedial Thalamus of People with Alcohol-Related Disorders.	Hade AC et al.	—	2021	→
Converging vulnerability factors for compulsive food and drug use.	Serafine KM et al.	—	2021	→
Cross-Disorder Genomics Data Analysis Elucidates a Shared Genetic Basis Between Major Depression and Osteoarthritis Pain.	Barowsky S et al.	—	2021	→
Dimensional Phenotypes in Psychiatric Genetics: Lessons from Genome-Wide Association Studies of Alcohol Use Phenotypes.	Mallard TT et al.	—	2021	→
Drinking and smoking polygenic risk is associated with childhood and early-adulthood psychiatric and behavioral traits independently of substance use and psychiatric genetic risk.	De Angelis F et al.	—	2021	→
Exploring the genetic overlap of suicide-related behaviors and substance use disorders.	Colbert SMC et al.	—	2021	→
Functional validation of a finding from a mouse genome-wide association study shows that Azi2 influences the acute locomotor stimulant response to methamphetamine.	Zhou X et al.	—	2021	→
Genes identified in rodent studies of alcohol intake are enriched for heritability of human substance use.	Huggett SB et al.	—	2021	→
Genetic basis of cannabis use: a systematic review.	Hillmer A et al.	—	2021	→
Genetic contributions to alcohol use disorder treatment outcomes: a genome-wide pharmacogenomics study.	Biernacka JM et al.	—	2021	→
Genetic Liability to Cannabis Use Disorder and COVID-19 Hospitalization.	Hatoum AS et al.	—	2021	→
Genetics of substance use disorders: a review.	Deak JD et al.	—	2021	→
Genetics of substance use disorders in the era of big data.	Gelernter J et al.	—	2021	→
Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology.	Mullins N et al.	—	2021	→
Integration of evidence across human and model organism studies: A meeting report.	Palmer RHC et al.	—	2021	→
Molecular genetics of substance use disorders: An umbrella review.	Lopez-Leon S et al.	—	2021	→
Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality.	Polimanti R et al.	—	2021	→
Multi-omics integration analysis identifies novel genes for alcoholism with potential overlap with neurodegenerative diseases.	Kapoor M et al.	—	2021	→
Novel characterization of the multivariate genetic architecture of internalizing psychopathology and alcohol use.	Colbert SMC et al.	—	2021	→
Nutritional Ketosis as a Potential Treatment for Alcohol Use Disorder.	Mahajan VR et al.	—	2021	→
Polygenic risk scores for alcohol involvement relate to brain structure in substance-naïve children: Results from the ABCD study.	Hatoum AS et al.	—	2021	→
Polygenic Score for Smoking is associated with Externalizing Psychopathology and Disinhibited Personality Traits but not Internalizing Psychopathology in Adolescence.	Hicks BM et al.	—	2021	→
Potential causal effect of posttraumatic stress disorder on alcohol use disorder and alcohol consumption in individuals of European descent: A Mendelian Randomization Study.	Bountress KE et al.	—	2021	→
Preclinical developments of enzyme-loaded red blood cells.	Rossi L et al.	—	2021	→
Prospective randomized pharmacogenetic study of topiramate for treating alcohol use disorder.	Kranzler HR et al.	—	2021	→
Sex-specific nicotine sensitization and imprinting of self-administration in rats inform GWAS findings on human addiction phenotypes.	Kozlova A et al.	—	2021	→
Stress-Responsive Gene FK506-Binding Protein 51 Mediates Alcohol-Induced Liver Injury Through the Hippo Pathway and Chemokine (C-X-C Motif) Ligand 1 Signaling.	Kusumanchi P 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	→
The patterns of family genetic risk scores for eleven major psychiatric and substance use disorders in a Swedish national sample.	Kendler KS et al.	—	2021	→
Using Mendelian randomization analysis to better understand the relationship between mental health and substance use: a systematic review.	Treur JL et al.	—	2021	→
Alcohol Sensitivity as an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility between Rodents and Humans.	Parker CC et al.	—	2020	→
Heterogeneity and Polygenicity in Psychiatric Disorders: A Genome-Wide Perspective.	Wendt FR et al.	—	2020	→
Identification of Functional Genetic Variants Associated With Alcohol Dependence and Related Phenotypes Using a High-Throughput Assay.	Thapa KS et al.	—	2020	→
Recent advances in genetic studies of alcohol use disorders.	Gupta I et al.	—	2020	→