Evidence map›Paper›PMID 30080747›Full record

ArticlePsychiatric genetics2018

Unravelling the GSK3β-related genotypic interaction network influencing hippocampal volume in recurrent major depressive disorder.

Becky Inkster, Andy Simmons, James H Cole, Erwin Schoof, Rune Linding, Tom Nichols, Pierandrea Muglia, Florian Holsboer, Philipp G Sämann, Peter McGuffin and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Psychiatric genetics, 2018. 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
–field-weighted citation impact
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. Review
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

15 authors.

Becky InksterDepartment of Psychiatry.
Andy SimmonsInstitute of Psychiatry, Psychology and Neuroscience, Kings College London.
James H ColeInstitute of Psychiatry, Psychology and Neuroscience, Kings College London.
Erwin SchoofBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen.
Rune LindingBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen.
Tom NicholsNuffield Department of Population Health, University of Oxford.
Pierandrea MugliaMedicine Development Centre, Genetics Division, Drug Discovery, GlaxoSmithKline, R&D, Verona, Italy.
Florian HolsboerMax Planck Institute Munich, Munich, Germany.
Philipp G SämannMax Planck Institute Munich, Munich, Germany.
Peter McGuffinInstitute of Psychiatry, Psychology and Neuroscience, Kings College London.
Cynthia H Y FuInstitute of Psychiatry, Psychology and Neuroscience, Kings College London.
Kamilla MiskowiakDepartment of Psychiatry, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Denmark.
Paul M MatthewsDepartment of Medicine, UK Dementia Research Institute, Imperial College London, London.
Gwyneth ZaiMolecular Brain Science Department, Neurogenetics Section, Centre for Addiction and Mental Health, Mood and Anxiety Division, Campbell Family Mental Health Research Institute.
Kristin NicodemusCentre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine.

Funding

CIHRMedical Research Council G0900897Medical Research Council G9409531Medical Research Council G9409634Medical Research Council G9901399Medical Research Council MC_PC_17114Medical Research Council MR/K501013/1Medical Research Council MR/N026934/1Wellcome Trust 100309
6 · The paper itself

Abstract

objectiveGlycogen synthase kinase 3β (GSK3β) has been implicated in mood disorders. We previously reported associations between a GSK3β polymorphism and hippocampal volume in major depressive disorder (MDD). We then reported similar associations for a subset of GSK3β-regulated genes. We now investigate an algorithm-derived comprehensive list of genes encoding proteins that directly interact with GSK3β to identify a genotypic network influencing hippocampal volume in MDD. PARTICIPANTS AND

methodsWe used discovery (N=141) and replication (N=77) recurrent MDD samples. Our gene list was generated from the NetworKIN database. Hippocampal measures were derived using an optimized Freesurfer protocol. We identified interacting single nucleotide polymorphisms using the machine learning algorithm Random Forest and verified interactions using likelihood ratio tests between nested linear regression models.

resultsThe discovery sample showed multiple two-single nucleotide polymorphism interactions with hippocampal volume. The replication sample showed a replicable interaction (likelihood ratio test: P=0.0088, replication sample; P=0.017, discovery sample; Stouffer's combined P=0.0007) between genes associated previously with endoplasmic reticulum stress, calcium regulation and histone modifications.

conclusionOur results provide genetic evidence supporting associations between hippocampal volume and MDD, which may reflect underlying cellular stress responses. Our study provides evidence of biological mechanisms that should be further explored in the search for disease-modifying therapeutic targets for depression.

Indexed as

AdultAgedAlgorithmsCase-Control StudiesDatabases, GeneticFemaleGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeGlycogen Synthase Kinase 3 betaHippocampusHumansMagnetic Resonance ImagingMajor Depressive DisorderMaleGlycogen Synthase Kinase 3 betaGSK3B protein, human

Identifiers

PMID30080747
PMCPMC6531290

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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.