Evidence map›Paper›PMID 27374936›Full record

ArticleAlcoholism, clinical and experimental research2016

Analysis of Rare Variants in the Alcohol Dependence Candidate Gene GATA4.

Franziska Degenhardt, Laurenz Krämer, Josef Frank, Jens Treutlein, Stefanie Heilmann-Heimbach, Julian Hecker, Heide Löhlein Fier, Maren Lang, Stephanie H Witt, Anna C Koller and 6 more

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

Article in Alcoholism, clinical and experimental research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 36% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Article
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

16 authors at 6 institutions in 2 countries.

Franziska DegenhardtInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Laurenz KrämerInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Josef FrankDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Jens TreutleinDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Stefanie Heilmann-HeimbachInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Julian HeckerInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Heide Löhlein FierInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Maren LangDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Stephanie H WittDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Anna C KollerInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Karl MannDepartment of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany.
Sabine HoffmannDepartment of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany.
Falk KieferDepartment of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany.
Rainer SpanagelInstitute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Marcella RietschelDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Markus M NöthenInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Heidelberg University · DELife & Brain (Germany) · DEUniversity Hospital Heidelberg · DEUniversity of Bonn · DECentral Institute of Mental Health · DEHarvard University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCommon variants in the gene GATA binding protein 4 (GATA4) show association with alcohol dependence (AD). The aim of this study was to identify rare variants in GATA4 in order to elucidate the role of this gene in AD susceptibility. Identification of rare variants may provide a more complete picture of the allelic architecture at this risk locus.

methodsSanger sequencing of all 6 coding exons of GATA4 was performed in 528 patients and 517 controls. Four in silico prediction tools were used to determine the effect of a DNA variant on the amino acid sequence and protein function. Five variants were included in the replication step. Of these, 4 were successfully genotyped in our replication cohort of 655 patients and 1,501 controls. All patients fulfilled DSM-IV criteria for AD, and all individuals were of German descent.

resultsIn the discovery step, 19 different heterozygous variants were identified. Four patient-specific and potentially functionally relevant variants were followed up. Only the variant S379S (c.1137C>T) remained patient specific (1/1,166 patients vs. 0/1,997 controls). None of the variants showed a statistically significant association with AD.

conclusionsThe present study elucidated the role of GATA4 in AD susceptibility by identifying rare variants via Sanger sequencing and subsequent replication. Although novel patient-specific rare variants of GATA4 were identified, none received support in the independent replication step. However, given previous robust findings of association with common variants, GATA4 remains a promising candidate gene for AD.

Indexed as

AdultAlcoholismCohort StudiesFemaleFollow-Up StudiesGATA4 Transcription FactorGenetic Association StudiesGenetic VariationHumansMaleMiddle AgedGATA4 protein, humanGATA4 Transcription FactorAlcohol DependenceCommon VariantsGATA4Genetic Risk FactorRare Variants

Identifiers

PMID27374936
PMCPMC5108491
OpenAlexW2464695470

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.