Evidence map›Paper›PMID 27572077›Full record

ArticleGenome biology2016

An integrated genetic-epigenetic analysis of schizophrenia: evidence for co-localization of genetic associations and differential DNA methylation.

Eilis Hannon, Emma Dempster, Joana Viana, Joe Burrage, Adam R Smith, Ruby Macdonald, David St Clair, Colette Mustard, Gerome Breen, Sebastian Therman and 14 more

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

Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers, 20 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
203citing papers in PubMed, 20 pooled it
20.5field-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

203 citing papers in PubMed, 20 syntheses or guidelines pooled it, 385 citations in OpenAlex.

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143 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 6 countries.

Eilis HannonUniversity of Exeter Medical School, University of Exeter, Exeter, UK.
Emma DempsterUniversity of Exeter Medical School, University of Exeter, Exeter, UK.
Joana VianaUniversity of Exeter Medical School, University of Exeter, Exeter, UK.
Joe BurrageUniversity of Exeter Medical School, University of Exeter, Exeter, UK.
Adam R SmithUniversity of Exeter Medical School, University of Exeter, Exeter, UK.
Ruby MacdonaldUniversity of Exeter Medical School, University of Exeter, Exeter, UK.
David St ClairThe Institute of Medical Sciences, Aberdeen University, Aberdeen, UK.
Colette MustardUniversity of the Highlands and Islands, Inverness, UK.
Gerome BreenInstitute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK.
Sebastian ThermanNational Institute for Health and Welfare, Helsinki, Finland.
Jaakko KaprioNational Institute for Health and Welfare, Helsinki, Finland.
Timothea ToulopoulouDepartment of Psychology, The University of Hong Kong, Pokfulam, Hong Kong.
Hilleke E Hulshoff PolDepartment of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Marc M BohlkenDepartment of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Rene S KahnDepartment of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Igor NenadicDepartment of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
Christina M HultmanDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
Robin M MurrayInstitute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK.
David A CollierInstitute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK.
Nick BassDivision of Psychiatry, University College London, London, UK.
Hugh GurlingDivision of Psychiatry, University College London, London, UK.
Andrew McQuillinDivision of Psychiatry, University College London, London, UK.
Leonard SchalkwykInstitute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK.
Jonathan MillUniversity of Exeter Medical School, University of Exeter, Exeter, UK. J.Mill@exeter.ac.uk.
University of Exeter · GBKing's College London · GBUniversity College London · GBUniversity Medical Center Utrecht · NLEli Lilly (United Kingdom) · GBFinnish Institute for Health and Welfare · FIInstitute for Molecular Medicine Finland · FIJena University Hospital · DEKarolinska Institutet · SERoyal Devon and Exeter Hospital · GBUniversity of Aberdeen · GBUniversity of Hong Kong · HKUniversity of the Highlands and Islands · GB

Funding

Neural Phenotypes for Schizophrenia and Bipolar DisorderR01MH052857 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI CANNON, TYRONE D · 1995 to 2010
$5.0M
A multi-faceted approach to epigenomic profiling in Alzheimer's disorderR01AG036039 · NIA · KING'S COLLEGE LONDON · PI MILL, JONATHAN · 2009 to 2012
$1.7M
Department of Health RP-PG-0606-1049Medical Research Council G0600972Medical Research Council G0700995Medical Research Council G1100583Medical Research Council MR/K004867/1Medical Research Council MR/K013807/1NIA NIH HHS R01 AG036039NIMH NIH HHS R01 MH052857
6 · The paper itself

Abstract

backgroundSchizophrenia is a highly heritable, neuropsychiatric disorder characterized by episodic psychosis and altered cognitive function. Despite success in identifying genetic variants associated with schizophrenia, there remains uncertainty about the causal genes involved in disease pathogenesis and how their function is regulated.

resultsWe performed a multi-stage epigenome-wide association study, quantifying genome-wide patterns of DNA methylation in a total of 1714 individuals from three independent sample cohorts. We have identified multiple differentially methylated positions and regions consistently associated with schizophrenia across the three cohorts; these effects are independent of important confounders such as smoking. We also show that epigenetic variation at multiple loci across the genome contributes to the polygenic nature of schizophrenia. Finally, we show how DNA methylation quantitative trait loci in combination with Bayesian co-localization analyses can be used to annotate extended genomic regions nominated by studies of schizophrenia, and to identify potential regulatory variation causally involved in disease.

conclusionsThis study represents the first systematic integrated analysis of genetic and epigenetic variation in schizophrenia, introducing a methodological approach that can be used to inform epigenome-wide association study analyses of other complex traits and diseases. We demonstrate the utility of using a polygenic risk score to identify molecular variation associated with etiological variation, and of using DNA methylation quantitative trait loci to refine the functional and regulatory variation associated with schizophrenia risk variants. Finally, we present strong evidence for the co-localization of genetic associations for schizophrenia and differential DNA methylation.

Indexed as

EpigenomicsBayes TheoremCpG IslandsDNA MethylationGenome-Wide Association StudyHumansMultifactorial InheritancePhenotypeQuantitative Trait LociSchizophreniaTwins, MonozygoticDNA methylationEpigeneticsEpigenome-wide association study (EWAS)GeneticsGenome-wide association study (GWAS)Polygenic risk score (PRS)Schizophrenia

Identifiers

PMID27572077
PMCPMC5004279
OpenAlexW2510420694

What OpenQuestion holds

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LicenceCC BY
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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.