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

Hannon, Eilis and Dempster, Emma L and Mansell, Georgina and Burrage, Joe and Bass, Nick and Bohlken, Marc M and Corvin, Aiden and Curtis, Charles J and Dempster, David and Di Forti, Marta and Dinan, Timothy G and Donohoe, Gary and Gaughran, Fiona and Gill, Michael and Gillespie, Amy and Gunasinghe, Cerisse and Hulshoff, Hilleke E and Hultman, Christina M and Johansson, Viktoria and Kahn, René S and Kaprio, Jaakko and Kenis, Gunter and Kowalec, Kaarina and MacCabe, James and McDonald, Colm and McQuillin, Andrew and Morris, Derek W and Murphy, Kieran C and Mustard, Colette J and Nenadic, Igor and O'Donovan, Michael C and Quattrone, Diego and Richards, Alexander L and Rutten, Bart Pf and St Clair, David and Therman, Sebastian and Toulopoulou, Timothea and Van Os, Jim and Waddington, John L and Wellcome Trust Case Control Consortium (WTCCC), and CRESTAR consortium, and Sullivan, Patrick and Vassos, Evangelos and Breen, Gerome and Collier, David Andrew and Murray, Robin M and Schalkwyk, Leonard S and Mill, Jonathan (2021) 'DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia.' eLife, 10. pp. 1-53. ISSN 2050-084X

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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.

Item Type: Article
Uncontrolled Keywords: Wellcome Trust Case Control Consortium (WTCCC); CRESTAR consortium
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 03 Dec 2021 16:31
Last Modified: 06 Jan 2022 14:22
URI: http://repository.essex.ac.uk/id/eprint/31693

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