Evidence map›Paper›PMID 22004471›Full record

ArticleAddiction biology2012

Genome-wide significant association between alcohol dependence and a variant in the ADH gene cluster.

Josef Frank, Sven Cichon, Jens Treutlein, Monika Ridinger, Manuel Mattheisen, Per Hoffmann, Stefan Herms, Norbert Wodarz, Michael Soyka, Peter Zill and 14 more

Open access · greenAbstract read
In one paragraph

Article in Addiction biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 12 pooled it
11.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

95 citing papers in PubMed, 12 syntheses or guidelines pooled it, 184 citations in OpenAlex.

  1. Pooled it
  2. Genome-wide meta-analysis of alcohol use disorder in East Asians.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022
    Pooled it
  3. Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020
    Pooled it
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  11. Association of gamma-aminobutyric acid A receptor α2 gene (GABRA2) with alcohol use disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014
    Pooled it
  12. Pooled it
  13. Trial
  14. Article
  15. Article
  16. Article
  17. Article
  18. Biochemical Diagnosis in Substance and Non-substance Addiction.Advances in experimental medicine and biology · 2025
    Review
  19. Review
  20. Human genetics and epigenetics of alcohol use disorder.The Journal of clinical investigation · 2024
    Review

35 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 13 institutions in 3 countries.

Josef FrankDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Germany.
Sven Cichon
Jens Treutlein
Monika Ridinger
Manuel Mattheisen
Per Hoffmann
Stefan Herms
Norbert Wodarz
Michael Soyka
Peter Zill
Wolfgang Maier
Rainald Mössner
Wolfgang Gaebel
Norbert Dahmen
Norbert Scherbaum
Christine Schmäl
Michael Steffens
Susanne Lucae
Marcus Ising
Bertram Müller-Myhsok
Markus M Nöthen
Karl Mann
Falk Kiefer
Marcella Rietschel
University of Bonn · DECentral Institute of Mental Health · DEHeidelberg University · DEMax Planck Institute of Psychiatry · DEUniversity of Regensburg · DEForschungszentrum Jülich · DEHarvard University · USHeinrich Heine University Düsseldorf · DEJohannes Gutenberg University Mainz · DELife & Brain (Germany) · DELudwig-Maximilians-Universität München · DEPrivatklinik Meiringen · CHUniversity of Duisburg-Essen · DE

Funding

Subject CollectionU10AA008401 · NIAAA · SUNY DOWNSTATE MEDICAL CENTER · PI JESSICA E SALVATORE · 1989 to 2026
$162.7M
JH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2M
Genetic Epidemiology of COPDU01HL089856 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2007 to 2021
$20.7M
The Collaborative Genetic Study of Nicotine DependenceP01CA089392 · NCI · WASHINGTON UNIVERSITY · PI BIERUT, LAURA J. · 2001 to 2012
$17.3M
PILOT--GENETIC EPIDEMIOLOGY OF ALCOHOL AND TOBACCO CONSUMPTION IN CHINESE SAMPLEP50AA011998 · NIAAA · WASHINGTON UNIVERSITY · PI SHER, KENNETH JAMES · 1999 to 2008
$12.6M
Resource CoreP60AA011998 · NIAAA · WASHINGTON UNIVERSITY · PI MADDEN, PAMELA ANN · 2009 to 2013
$8.8M
Genome Wide Association Coordinating CenterU01HG004446 · NHGRI · UNIVERSITY OF WASHINGTON · PI WEIR, BRUCE S. · 2007 to 2011
$6.6M
Molecular Epidemiology of Alcoholism 2- Big SibshipsR01AA013320 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 2003 to 2007
$3.1M
FAMILY STUDY OF COCAINE DEPENDENCER01DA013423 · NIDA · WASHINGTON UNIVERSITY · PI BIERUT, LAURA JEAN · 2000 to 2004
$2.2M
Novel Statistical Approaches to Mental Health Phenotype Analysis in GWA StudiesR01MH081862 · NIMH · HARVARD SCHOOL OF PUBLIC HEALTH · PI LANGE, CHRISTOPH · 2009 to 2014
$2.0M
A New Approach to Mental Health Phenotypes in Family Genomewide AssociationR01MH087590 · NIMH · HARVARD SCHOOL OF PUBLIC HEALTH · PI LANGE, CHRISTOPH · 2010 to 2013
$1.6M
Study of Addiction: Genetics and EnvironmentU01HG004422 · NHGRI · WASHINGTON UNIVERSITY · PI BIERUT, LAURA J. · 2007 to 2010
$1.2M
NCI NIH HHS P01 CA089392NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS U01 HG004422NHGRI NIH HHS U01HG004422NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01HG004438NHGRI NIH HHS U01 HG004446NHLBI NIH HHS U01 HL089856NIAAA NIH HHS 5 R01 AA013320-04NIAAA NIH HHS P50 AA011998NIAAA NIH HHS P60 AA011998NIAAA NIH HHS P60 AA011998-11NIAAA NIH HHS R01 AA013320NIAAA NIH HHS U10 AA008401NIAAA NIH HHS U10AA008401NIDA NIH HHS R01 DA013423NIMH NIH HHS R01 MH081862NIMH NIH HHS R01 MH087590
6 · The paper itself

Abstract

Alcohol dependence (AD) is an important contributory factor to the global burden of disease. The etiology of AD involves both environmental and genetic factors, and the disorder has a heritability of around 50%. The aim of the present study was to identify susceptibility genes for AD by performing a genome-wide association study (GWAS). The sample comprised 1333 male in-patients with severe AD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and 2168 controls. These included 487 patients and 1358 controls from a previous GWAS study by our group. All individuals were of German descent. Single-marker tests and a polygenic score-based analysis to assess the combined contribution of multiple markers with small effects were performed. The single nucleotide polymorphism (SNP) rs1789891, which is located between the ADH1B and ADH1C genes, achieved genome-wide significance [P = 1.27E-8, odds ratio (OR) = 1.46]. Other markers from this region were also associated with AD, and conditional analyses indicated that these made a partially independent contribution. The SNP rs1789891 is in complete linkage disequilibrium with the functional Arg272Gln variant (P = 1.24E-7, OR = 1.31) of the ADH1C gene, which has been reported to modify the rate of ethanol oxidation to acetaldehyde in vitro. A polygenic score-based approach produced a significant result (P = 9.66E-9). This is the first GWAS of AD to provide genome-wide significant support for the role of the ADH gene cluster and to suggest a polygenic component to the etiology of AD. The latter result may indicate that many more AD susceptibility genes still await identification.

Indexed as

AdultAlcohol DehydrogenaseAlcoholismGenome-Wide Association StudyGermanyHumansMaleMultigene FamilyOdds RatioPolymorphism, Single NucleotideADH1B protein, humanADH1C protein, humanAlcohol Dehydrogenase

Identifiers

PMID22004471
PMCPMC3245349
OpenAlexW1585065066

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.