Alcohol Dependence Genetics: Lessons Learned From Genome-Wide Association Studies (GWAS) and Post-GWAS Analyses.

paper Cited Public

Authors: Hart, Amy B; Kranzler, Henry R
Year: 2015
Journal: Alcoholism, clinical and experimental research
PMID: 26110981
DOI: 10.1111/acer.12792
PMCID: PMC4515198

#	Section	Preview
0	Introduction	Alcohol dependence (AD) is a common, complex psychiatric disorder characterized by the excessive and…
1	Introduction	Early evidence that AD has a genetic component came from studies showing significant familial…
2	Introduction	Significant advances in the identification of risk loci for AD in the past decade can be largely…
3	Introduction	Here we summarize findings from all identified published classical GWAS of AD, discuss the knowledge…
4	Genome-wide association studies	Genome-wide linkage and candidate gene association studies (reviewed by Agrawal and Bierut, 2012;…
5	Genome-wide association studies	genome-wide association study (GWAS) approach was proposed to identify loci associated with complex…
6	Genome-wide association studies	that, for the majority of complex traits, much larger samples are needed to achieve the statistical…
7	Findings from classical AD GWAS	Table 1 provides an overview of the 12 published AD GWAS. The first GWAS of AD was published in 2009…
8	Findings from classical AD GWAS	Bierut et al. (2010) performed a GWAS of AD in the Study of Addiction: Genetics and Environment…
9	Findings from classical AD GWAS	Edenberg et al. (2010) performed a GWAS using over 800,000 SNPs in a family-based sample of 847 AD…
10	Findings from classical AD GWAS	Kendler et al. (2011) performed an AD GWAS in a population-based sample of 2,357 EAs and 812 AAs…
11	Findings from classical AD GWAS	In one of the largest AD GWAS to date, Heath et al. (2011) included 8,754 European ancestry family…
12	Findings from classical AD GWAS	Frank et al. (2012) performed a GWAS with over 400,000 SNPs in a German sample of 1,333 men with…
13	Findings from classical AD GWAS	Zuo et al. (2012) performed an AD meta-analysis in the SAGE and COGA datasets (1,409 EA AD cases,…
14	Findings from classical AD GWAS	Wang et al. (2013) performed an AD GWAS with approximately 600,000 SNPs in an expanded COGA sample…
15	Findings from classical AD GWAS	McGue et al. (2013) performed an AD GWAS of “behavioral disinhibition” traits including AD and…
16	Findings from classical AD GWAS	Park et al. (2013) conducted an AD GWAS in 117 Korean AD cases and 279 Korean controls, testing for…
17	Findings from classical AD GWAS	Quillen et al. (2014) performed an AD GWAS in 102 Chinese male AD cases and 212 Chinese male…
18	Findings from classical AD GWAS	The largest AD GWAS to date was performed by Gelernter et al. (2014a). The discovery sample…
19	Findings from classical AD GWAS	Gelernter et al., 2014c) and the analysis by Wang et al. (2013), the authors tested for association…

Name	Type
39-gene subnetwork local	gene
AA	cohort
AD-associated genes local	gene
AD case-control phenotype local	phenotype
AD case-control status local	phenotype
AD criterion factor score local	phenotype
addiction	phenotype
AD GWAS	cohort
ADH1B	gene
ADH1C	gene
ADH7	gene
AD risk	phenotype
African American	cohort
African-Americans	cohort
African-ancestry populations local	cohort
age-related macular degeneration	phenotype
AKAP9 local	gene
alcohol	phenotype
alcohol abuse	phenotype
alcohol dependence	phenotype
Alcohol-exposed controls local	cohort
Alcohol metabolizing enzyme genes local	gene
Alcohol Use	phenotype
ALDH2	gene
Alzheimer's disease	phenotype
Asian	cohort
Australian population-based controls local	cohort
behavioral disinhibition	phenotype
Bierut et al. 2010 GWAS local	cohort
bipolar disorder	phenotype
body mass index	phenotype
CAST	gene
causal risk variants local	variant
CCD41 local	gene
CDH13	gene
Chinese male AD cases local	cohort
Chinese male controls local	cohort
cocaine	phenotype
COGA dataset	cohort
COGA discovery local	cohort
COGA sample	cohort
Collaborative Study on the Genetics of Alcoholism (COGA)	cohort
common variants	cohort
complex traits	phenotype
COMT	gene
DBP local	gene
discovery sample	cohort
disease susceptibility	phenotype
Do et al. 2012 study local	cohort
DRD2	gene
Drosophila knockdown model local	cohort
DSM diagnosis-based phenotype local	phenotype
DSM-IV AD criterion count phenotype local	phenotype
DSM-IV alcohol dependence	phenotype
DSM-IV criterion count phenotype local	phenotype
EA	cohort
early onset alcohol dependence	phenotype
East Asian	cohort
Edenberg et al. 2010 GWAS local	cohort
ERAP1	gene
ESR1	gene
ethanol consumption	phenotype
European-American populations local	cohort
European ancestry	cohort
European ancestry family members local	cohort
European OZALC GWAS sample local	cohort
European population	cohort
exfoliation glaucoma	phenotype
Extended pedigrees enriched for AD local	cohort
Flushing response	phenotype
Full offspring sample local	cohort
full sample	cohort
GATA4	gene
German GWAS dataset local	cohort
German GWAS sample local	cohort
German men cohort (2009) local	cohort
German sample	cohort
German target sample local	cohort
Glutamate receptor	drug
GRIK1	gene
GSCAN	cohort
GWAS & Sequencing Consortium of Alcohol and Nicotine use	cohort
Heath et al. 2011 AD GWAS local	cohort
height	phenotype
High risk Alcohol Dependence local	phenotype
Htr1a	gene
HTR1A SNP local	variant
Illicit drug phenotypes local	phenotype
illicit drug use	phenotype
intermediate phenotypes	phenotype
ketone bodies	drug
KIAA0040	gene
KIAA0040 SNPs local	variant
Korean AD cohort local	cohort
loci	cohort
major psychiatric disorders	phenotype
Maximum blood alcohol concentration local	phenotype
Maximum drinks consumed in 24-hour period local	phenotype
MCTFR	cohort
Molecular Genetics of Schizophrenia (MGS2) control sample	cohort
multiple sclerosis	phenotype
NALCN	gene
NALCN SNP local	variant
National Epidemiologic Survey on Alcohol and Related Conditions	cohort
nicotine	drug
nicotine dependence	phenotype
nicotine use	phenotype
NIMH Research Domain Criteria (RDoC) Project local	cohort
non-European ancestry	cohort
opioid	drug
opioid dependence	phenotype
OPRM1	cohort
PECR	gene
PGC Addictions group local	cohort
PGC dataset	cohort
phenotypic variance	phenotype
PIGG local	gene
PITRM1 local	gene
PPP2R2B	gene
Psychiatric Genomics Consortium	cohort
quantitative AD factor score local	phenotype
quantitative heaviness of drinking factor score local	phenotype
rare variant	cohort
rheumatoid arthritis	phenotype
rs10516441 local	variant
rs1229984	variant
rs13160562	variant
rs1442492 local	variant
rs1693482	variant
rs1789891	variant
rs2066702	variant
rs3782886	variant
rs671	variant
rs828701 local	variant
SAGE	cohort
SAGE dataset	cohort
SAGE EA	cohort
SAGE_EA local	cohort
SAGE target samples local	cohort
samples	cohort
schizophrenia	phenotype
SERINC2	gene
SERINC2 SNPs	variant
SNP	cohort
SNP heritability signal local	phenotype
Study of Addiction: Genetics and Environment (SAGE) sample local	cohort
Subsample of twins local	cohort
substance abuse	phenotype
topiramate	drug
top SNPs	cohort
Treuitlen et al. 2009 sample local	cohort
Treutlein et al. 2009 GWAS	cohort
type 2 diabetes	phenotype
United States alcohol abuse and dependence samples local	cohort
Unrelated offspring sample local	cohort
Unrelated parent sample local	cohort
XRCC5	gene
Yale-Penn	cohort
Yale-Penn sample	cohort
Yang et al. 2014 study local	cohort

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In this knowledge base

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Allele-specific expression and high-throughput reporter assay reveal functional genetic variants associated with alcohol use disorders.	2021	31477794
Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations.	2019	30940813
Incorporating Functional Genomic Information to Enhance Polygenic Signal and Identify Variants Involved in Gene-by-Environment Interaction for Young Adult Alcohol Problems.	2018	29121402
Polygenic Risk Score Prediction of Alcohol Dependence Symptoms Across Population-Based and Clinically Ascertained Samples.	2018	29405378
Deep Sequencing of 71 Candidate Genes to Characterize Variation Associated with Alcohol Dependence.	2017	28196272
The utility of empirically assigning ancestry groups in cross-population genetic studies of addiction.	2017	28714599
Validating Harmful Alcohol Use as a Phenotype for Genetic Discovery Using Phosphatidylethanol and a Polymorphism in ADH1B.	2017	28295416
Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations.	2017	28981154
Genetic influences on adolescent behavior.	2016	27422449

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Ethanol-Related Behaviors in Mouse Lines Selectively Bred for Drinking to Intoxication.	Jensen BE et al.	—	2021	→
Gender Differences among Sardinians with Alcohol Use Disorder.	Agabio R et al.	—	2021	→
Genetic variants of <i>EML1</i> and <i>HIST1H4E</i> in myeloid cell-related pathway genes independently predict cutaneous melanoma-specific survival.	He Y et al.	—	2021	→
Identifying a novel biological mechanism for alcohol addiction associated with circRNA networks acting as potential miRNA sponges.	Vornholt E et al.	—	2021	→
Long tracks of homozygosity predict the severity of alcohol use disorders in an American Indian population.	Peng Q et al.	—	2021	→
Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction.	Karlsson Linnér R et al.	—	2021	→
Proteomic Signatures of Lifestyle Risk Factors for Cardiovascular Disease: A Cross-Sectional Analysis of the Plasma Proteome in the Framingham Heart Study.	Corlin L et al.	—	2021	→
The influence of regression models on genome-wide association studies of alcohol dependence: a comparison of binary and quantitative analyses.	Li W et al.	—	2021	→
The Vista of Application of Specific Anaphylaxis Accurate Diagnosis Based on DNA Single-Nucleotide Methylation Sites.	Guo X et al.	—	2021	→
Alcohol Cue-Induced Ventral Striatum Activity Predicts Subsequent Alcohol Self-Administration.	Lim AC 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	→
Association of relative brain age with tobacco smoking, alcohol consumption, and genetic variants.	Ning K et al.	—	2020	→
Differential sensitivity of human neurons carrying μ opioid receptor (MOR) N40D variants in response to ethanol.	Scarnati MS et al.	—	2020	→
Flying Together: <i>Drosophila</i> as a Tool to Understand the Genetics of Human Alcoholism.	Lathen DR et al.	—	2020	→
GRM8 genotype is associated with externalizing disorders and greater inter-trial variability in brain activation during a response inhibition task.	Bauer LO 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	→
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	→
Selective alterations in endogenous opioid system genes expression in rats selected for high ethanol intake during adolescence.	Bellia F et al.	—	2020	→
Beyond genome-wide significance: integrative approaches to the interpretation and extension of GWAS findings for alcohol use disorder.	Salvatore JE et al.	—	2019	→
Contributions of an Internalizing Symptoms Polygenic Risk Score and Contextual Factors to Alcohol-Related Disorders in African American Young Adults.	Rabinowitz JA et al.	—	2019	→
Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data.	Mignogna KM et al.	—	2019	→
Cross-Species Co-analysis of Prefrontal Cortex Chronic Ethanol Transcriptome Responses in Mice and Monkeys.	Bogenpohl JW et al.	—	2019	→
Genes, Roommates, and Residence Halls: A Multidimensional Study of the Role of Peer Drinking on College Students' Alcohol Use.	Smith RL et al.	—	2019	→
Genetic loci for alcohol-related life events and substance-induced affective symptoms: indexing the "dark side" of addiction.	Peng Q et al.	—	2019	→
Genetics of alcohol use disorder: a review.	Deak JD et al.	—	2019	→
Genetic Studies of Tic Disorders and Tourette Syndrome.	Qi Y et al.	—	2019	→
Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria.	Lai D 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 alcohol use disorder identification test (AUDIT) scores in 20 328 research participants of European ancestry.	Sanchez-Roige S et al.	—	2019	→
GWAS of Behavioral Traits.	Mehta D et al.	—	2019	→
Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial.	Roche DJO et al.	—	2019	→
Molecular tools to elucidate factors regulating alcohol use.	Logrip ML	—	2019	→
Paternal Preconception Every-Other-Day Ethanol Drinking Alters Behavior and Ethanol Consumption in Offspring.	Beeler E et al.	—	2019	→
Pharmacogenetics of alcohol use disorder treatments: an update.	Hartwell EE et al.	—	2019	→
The association between the FTO gene variant and alcohol consumption and binge and problem drinking in different gene-environment background: The HAPIEE study.	Hubacek JA et al.	—	2019	→
The Family Check-up Intervention Moderates Polygenic Influences on Long-Term Alcohol Outcomes: Results from a Randomized Intervention Trial.	Kuo SI et al.	—	2019	→
Unpacking Genetic Risk Pathways for College Student Alcohol Consumption: The Mediating Role of Impulsivity.	Ksinan AJ et al.	—	2019	→
"Why did I get that part of you?" Understanding addiction genetics through family history.	Dingel MJ 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	→
Curtailing the communicability of psychiatric disorders.	Wainberg ML et al.	—	2018	→
GABA<sub>A</sub> receptor polymorphisms in alcohol use disorder in the GWAS era.	Koulentaki M et al.	—	2018	→
Incorporating Functional Genomic Information to Enhance Polygenic Signal and Identify Variants Involved in Gene-by-Environment Interaction for Young Adult Alcohol Problems.	Salvatore JE et al.	—	2018	→
Polygenic Risk Score Prediction of Alcohol Dependence Symptoms Across Population-Based and Clinically Ascertained Samples.	Savage JE et al.	—	2018	→
Research Review: What have we learned about adolescent substance use?	Gray KM et al.	—	2018	→
Severity of alcohol dependence is associated with the fatty acid amide hydrolase Pro129Thr missense variant.	Sloan ME et al.	—	2018	→
Shaping vulnerability to addiction - the contribution of behavior, neural circuits and molecular mechanisms.	Egervari G et al.	—	2018	→
Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders.	Walters RK et al.	—	2018	→
Alcohol and nicotine codependence-associated DNA methylation changes in promoter regions of addiction-related genes.	Xu H et al.	—	2017	→
Alcohol Misuse Across the Lifespan: Insights from Developmental Studies in Behavior Genetics.	Savage JE et al.	—	2017	→
Bivariate genome-wide association analyses identified genetic pleiotropic effects for bone mineral density and alcohol drinking in Caucasians.	Lu S et al.	—	2017	→
Blunted Dopamine Transmission in Addiction: Potential Mechanisms and Implications for Behavior.	Trifilieff P et al.	—	2017	→
Deep Sequencing of 71 Candidate Genes to Characterize Variation Associated with Alcohol Dependence.	Clark SL et al.	—	2017	→
Genes, Environments, and Sex Differences in Alcohol Research.	Salvatore JE et al.	—	2017	→
Genetic studies of alcohol dependence in the context of the addiction cycle.	Reilly MT et al.	—	2017	→
Genome-wide association study of Alcohol Use Disorder Identification Test (AUDIT) scores in 20,328 research participants of European ancestry	Sanchez-Roige S et al.	—	2017	—
"I don't have to know why it snows, I just have to shovel it!": Addiction Recovery, Genetic Frameworks, and Biological Citizenship.	Dingel MJ et al.	—	2017	→
Stability and change in etiological factors for alcohol use disorder and major depression.	Torvik FA et al.	—	2017	→
The utility of empirically assigning ancestry groups in cross-population genetic studies of addiction.	Peterson RE et al.	—	2017	→
Validating Harmful Alcohol Use as a Phenotype for Genetic Discovery Using Phosphatidylethanol and a Polymorphism in ADH1B.	Justice AC et al.	—	2017	→
Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations.	Mathies LD et al.	—	2017	→
Contributions of mobile technologies to addiction research.	Swendsen J	—	2016	→
Genetic influences on adolescent behavior.	Dick DM et al.	—	2016	→
Genetics of Substance Use Disorders.	Yu C et al.	—	2016	→