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DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia

Authors: Eilis Hannon; Emma Dempster; Georgina Mansell; Joe Burrage; Nick Bass; Marc M. Bohlken; Aiden Corvin; +39 Authors

DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia

Abstract

We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.

Countries
Turkey, Netherlands, Finland, Sweden
Subjects by Vocabulary

Microsoft Academic Graph classification: Bioinformatics Clozapine Schizophrenia Meta-analysis DNA methylation medicine.drug Psychosis medicine.drug_class Atypical antipsychotic medicine Epigenetics Genetic association business.industry medicine.disease business

Keywords

Male, BLOOD, HIGH-POTENCY CANNABIS, DISEASE, Epigenome, WIDE ASSOCIATION, genetics, psychosis, Biology (General), Psychiatry, RISK, DNA methylation, clozapine, General Neuroscience, Q, R, General Medicine, Middle Aged, TRAIT, England, Medicine, HUMAN BRAIN-TISSUE, Female, BURDEN, Medical Genetics, Schizophrenia, Treatment-Resistant, Research Article, Human, Adult, QH301-705.5, Science, METHYLOMIC VARIATION, Psykiatri, General Biochemistry, Genetics and Molecular Biology, Young Adult, genomics, Humans, human, 1ST-EPISODE PSYCHOSIS, Medicinsk genetik, Aged, Sweden, epigenetics, General Immunology and Microbiology, Genetics and Genomics, schizophrenia, Psychotic Disorders, Scotland, 3111 Biomedicine, Ireland

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    download downloads 16
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    32
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
downloads
OpenAIRE UsageCountsDownloads provided by UsageCounts
32
Top 10%
Average
Top 10%
16
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gold
Funded byView all
EC| EU-GEI
Project
EU-GEI
European Network of National Schizophrenia Networks Studying Gene-Environment Interactions
  • Funder: European Commission (EC)
  • Project Code: 241909
  • Funding stream: FP7 | SP1 | HEALTH
,
EC| CRESTAR
Project
CRESTAR
Pharmacogenomic biomarkers as clinical decision making tools for clozapine treatment of schizophrenia
  • Funder: European Commission (EC)
  • Project Code: 279227
  • Funding stream: FP7 | SP1 | HEALTH
iis
,
WT| WTCCC2 core activities
Project
  • Funder: Wellcome Trust (WT)
  • Project Code: 085475
  • Funding stream: Genetics, Genomics and Population Research
iis
,
AKA| Center of Excellence in Complex Disease Genetics-from Discovery to Precision Medicine / Consortium: CoECDG
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Sustainable Development Solutions Network - Greece
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