Evidence map›Paper›PMID 25035082›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015

XRCC5 as a risk gene for alcohol dependence: evidence from a genome-wide gene-set-based analysis and follow-up studies in Drosophila and humans.

Dilafruz Juraeva, Jens Treutlein, Henrike Scholz, Josef Frank, Franziska Degenhardt, Sven Cichon, Monika Ridinger, Manuel Mattheisen, Stephanie H Witt, Maren Lang and 24 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 30% 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

9 citing papers in PubMed, 14 citations in OpenAlex.

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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

34 authors at 18 institutions in 4 countries.

Dilafruz JuraevaDivision of Theoretical Bioinformatics, German Cancer Research Center, Heidelberg, Germany.
Jens TreutleinDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Henrike ScholzDepartment of Animal Physiology, University of Cologne, Cologne, Germany.
Josef FrankDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Franziska Degenhardt1] Institute of Human Genetics, University of Bonn, Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Sven CichonDepartment of Biomedicine, University Hospital Basel, Basel, Switzerland.
Monika RidingerDepartment of Psychiatry, University of Regensburg, Regensburg, Germany.
Manuel MattheisenDepartment of Biomedicine, University of Aarhus, Denmark.
Stephanie H WittDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Maren LangDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Wolfgang H SommerInstitute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Per HoffmannDepartment of Biomedicine, University Hospital Basel, Basel, Switzerland.
Stefan HermsDepartment of Biomedicine, University Hospital Basel, Basel, Switzerland.
Norbert WodarzDepartment of Psychiatry, University of Regensburg, Regensburg, Germany.
Michael Soyka1] Private Hospital Meiringen, Meiringen, Switzerland [2] Department of Psychiatry, University of Munich, Munich, Germany.
Peter ZillDepartment of Psychiatry, University of Munich, Munich, Germany.
Wolfgang MaierDepartment of Psychiatry, University of Bonn, Bonn, Germany.
Elisabeth JüngerDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden.
Wolfgang GaebelDepartment of Psychiatry and Psychotherapy, University of Düsseldorf, Düsseldorf, Germany.
Norbert DahmenDepartment of Psychiatry, University of Mainz, Mainz, Germany.
Norbert ScherbaumAddiction Research Group at the Department of Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany.
Christine SchmälDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Michael SteffensDivision of Research, Federal Institute for Drugs and Medical Devices, Bonn, Germany.
Susanne LucaeDepartment of Psychiatric Pharmacogenetics, Max-Planck-Institute of Psychiatry, München, Germany.
Marcus IsingDepartment of Molecular Psychology, Max-Planck-Institute of Psychiatry, München, Germany.
Michael N SmolkaDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden.
Ulrich S ZimmermannDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden.
Bertram Müller-Myhsok1] Department of Statistical Genetics, Max-Planck-Institute of Psychiatry, München, Germany [2] Munich Cluster for Systems Neurology (SyNergy), Munich, Germany [3] Institute of Translational Medicine Liverpool, University of Liverpool, Liverpool, UK.
Markus M Nöthen1] Institute of Human Genetics, University of Bonn, Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Karl MannDepartment of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Falk KieferDepartment of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Rainer SpanagelInstitute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Benedikt BrorsDivision of Theoretical Bioinformatics, German Cancer Research Center, Heidelberg, Germany.
Marcella RietschelDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Heidelberg University · DECentral Institute of Mental Health · DEMax Planck Institute of Psychiatry · DEUniversity Hospital Heidelberg · DEUniversity Hospital of Basel · CHUniversity Hospital Carl Gustav Carus · DEUniversity of Bonn · DEUniversity of Regensburg · DEAarhus University · DKFederal Institute for Drugs and Medical Devices · DEHeinrich Heine University Düsseldorf · DEJohannes Gutenberg University Mainz · DELife & Brain (Germany) · DELudwig-Maximilians-Universität München · DEPrivatklinik Meiringen · CHTU Dresden · DEUniversity of Cologne · DEUniversity of Duisburg-Essen · DE

Funding

Collaboration on Alcohol Self-Administration in Adolescents and Young AdultsU01AA017900 · NIAAA · INDIANA UNIVERSITY INDIANAPOLIS · PI O'CONNOR, SEAN JOSEPH · 2009 to 2012
$1.1M
NIAAA NIH HHS 1U01AA017900-01
6 · The paper itself

Abstract

Genetic factors have as large role as environmental factors in the etiology of alcohol dependence (AD). Although genome-wide association studies (GWAS) enable systematic searches for loci not hitherto implicated in the etiology of AD, many true findings may be missed owing to correction for multiple testing. The aim of the present study was to circumvent this limitation by searching for biological system-level differences, and then following up these findings in humans and animals. Gene-set-based analysis of GWAS data from 1333 cases and 2168 controls identified 19 significantly associated gene-sets, of which 5 could be replicated in an independent sample. Clustered in these gene-sets were novel and previously identified susceptibility genes. The most frequently present gene, ie in 6 out of 19 gene-sets, was X-ray repair complementing defective repair in Chinese hamster cells 5 (XRCC5). Previous human and animal studies have implicated XRCC5 in alcohol sensitivity. This phenotype is inversely correlated with the development of AD, presumably as more alcohol is required to achieve the desired effects. In the present study, the functional role of XRCC5 in AD was further validated in animals and humans. Drosophila mutants with reduced function of Ku80-the homolog of mammalian XRCC5-due to RNAi silencing showed reduced sensitivity to ethanol. In humans with free access to intravenous ethanol self-administration in the laboratory, the maximum achieved blood alcohol concentration was influenced in an allele-dose-dependent manner by genetic variation in XRCC5. In conclusion, our convergent approach identified new candidates and generated independent evidence for the involvement of XRCC5 in alcohol dependence.

Indexed as

Genetic Predisposition to DiseaseAdolescentAlcoholismAnimalsAnimals, Genetically ModifiedCentral Nervous System DepressantsDNA HelicasesDrosophila melanogasterEthanolFemaleFollow-Up StudiesGenome-Wide Association StudyGermanyHumansKu AutoantigenMaleCentral Nervous System DepressantsDNA HelicasesEthanolKu AutoantigenXRCC5 protein, human

Identifiers

PMID25035082
PMCPMC4443948
OpenAlexW2006937454

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.