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

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Wellcome Trust Case Control Consor , CRESTAR Consortium , Hannon , E , Dempster , E L , Mansell , G , Kaprio , J & Mill , J 2021 , ' DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia ' , eLife , vol. 10 , 58430 . https://doi.org/10.7554/eLife.58430

Title: DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia
Author: Wellcome Trust Case Control Consor; CRESTAR Consortium; Hannon, Eilis; Dempster, Emma L.; Mansell, Georgina; Kaprio, Jaakko; Mill, Jonathan
Contributor organization: Institute for Molecular Medicine Finland
Department of Public Health
University of Helsinki
Date: 2021-02-26
Language: eng
Number of pages: 31
Belongs to series: eLife
ISSN: 2050-084X
DOI: https://doi.org/10.7554/eLife.58430
URI: http://hdl.handle.net/10138/330914
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.
Subject: 3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: acceptedVersion


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