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

Hannon, E; Dempster, EL; Mansell, G; Burrage, J; Bass, N; Bohlken, MM; Corvin, A; ... Mill, J; + view all (2021) DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia. eLife , 10 , Article e58430. 10.7554/eLife.58430. (In press). Green open access

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Abstract

We performed a systematic analysis of blood DNA methylation profiles from 4,483 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 1,048 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.

Type: Article
Title: DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.58430
Publisher version: https://doi.org/10.7554/eLife.58430
Language: English
Additional information: Copyright © 2021, Hannon et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) permitting unrestricted use and redistribution provided that the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
URI: https://discovery.ucl.ac.uk/id/eprint/10123612
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