Literature DB >> 33646943

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

Eilis Hannon1, Emma L Dempster1, Georgina Mansell1, Joe Burrage1, Nick Bass2, Marc M Bohlken3, Aiden Corvin4, Charles J Curtis5,6, David Dempster5, Marta Di Forti5,7,8, Timothy G Dinan9, Gary Donohoe10, Fiona Gaughran11,12, Michael Gill13, Amy Gillespie11,14, Cerisse Gunasinghe5, Hilleke E Hulshoff15, Christina M Hultman16, Viktoria Johansson17,18, René S Kahn19,20, Jaakko Kaprio21,22, Gunter Kenis23, Kaarina Kowalec16,24, James MacCabe5, Colm McDonald25, Andrew McQuillin2,2, Derek W Morris10, Kieran C Murphy26, Colette J Mustard27, Igor Nenadic28,29, Michael C O'Donovan30, Diego Quattrone5,7, Alexander L Richards30, Bart Pf Rutten31, David St Clair32, Sebastian Therman33, Timothea Toulopoulou34, Jim Van Os19, John L Waddington35, Patrick Sullivan16,36, Evangelos Vassos5, Gerome Breen5,6, David Andrew Collier37, Robin M Murray38, Leonard S Schalkwyk39, Jonathan Mill1.   

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.
© 2021, Hannon et al.

Entities:  

Keywords:  DNA methylation; clozapine; epigenetics; genetics; genomics; human; psychosis; schizophrenia

Mesh：

Year:  2021        PMID： 33646943      PMCID： PMC8009672          DOI： 10.7554/eLife.58430

Source DB:  PubMed          Journal:  Elife        ISSN： 2050-084X            Impact factor:   8.140


  79 in total

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