Authors:
Eilis Hannon, Emma Dempster, Georgina Mansell, Joe Burrage, Nick Bass, Marc M. Bohlken, Aiden Corvin, Charles Curtis, Charles Curtis, David Dempster, Marta Di Forti, Marta Di Forti, Marta Di Forti, Timothy G. Dinan, Gary Donohoe, Fiona Gaughran, Fion (...)
Eilis Hannon, Emma Dempster, Georgina Mansell, Joe Burrage, Nick Bass, Marc M. Bohlken, Aiden Corvin, Charles Curtis, Charles Curtis, David Dempster, Marta Di Forti, Marta Di Forti, Marta Di Forti, Timothy G. Dinan, Gary Donohoe, Fiona Gaughran, Fiona Gaughran, Michael Gill, Amy Gillespie, Amy Gillespie, Cerisse Gunasinghe, Hilleke E Hulshoff, Christina M. Hultman, Viktoria Johansson, René S. Kahn, René S. Kahn, Jaakko Kaprio, Gunter Kenis, Kaarina Kowalec, Kaarina Kowalec, James H. MacCabe, Colm McDonald, Andrew McQuillin, Derek W. Morris, Kieran C. Murphy, Colette J Mustard, Igor Nenadic, Michael Conlon O'Donovan, Diego Quattrone, Diego Quattrone, Alexander Richards, Bart P. F. Rutten, David St Clair, Sebastian Therman, Timothea Toulopoulou, Jim van Os, John L. Waddington, Patrick F. Sullivan, Patrick F. Sullivan, Evangelos Vassos, Gerome Breen, Gerome Breen, David A. Collier, Robin M. Murray, Leonard S. Schalkwyk, Jonathan Mill
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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 pipeli (...)
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.
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