TY - JOUR
T1 - Dna methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia
AU - CRESTAR consortium
AU - Wellcome Trust Case Control Consortium 2
AU - Hannon, Eilis
AU - Dempster, Emma L.
AU - Mansell, Georgina
AU - Burrage, Joe
AU - Bass, Nick
AU - Bohlken, Marc M.
AU - Corvin, Aiden
AU - Curtis, Charles J.
AU - Dempster, David
AU - Di Forti, Marta
AU - Dinan, Timothy G.
AU - Donohoe, Gary
AU - Gaughran, Fiona
AU - Gill, Michael
AU - Gillespie, Amy
AU - Gunasinghe, Cerisse
AU - Hulshoff, Hilleke E.
AU - Hultman, Christina M.
AU - Johansson, Viktoria
AU - Kahn, Rene S.
AU - Kaprio, Jaakko
AU - Kenis, Gunter
AU - Kowalec, Kaarina
AU - Maccabe, James
AU - McDonald, Colm
AU - McQuillin, Andew
AU - Morris, Derek W.
AU - Murphy, Kieran C.
AU - Mustard, Collette
AU - Nenadic, Igor
AU - O'donovan, Michael C.
AU - Quattrone, Diego
AU - Richards, Alexander L.
AU - Rutten, Bart P.F.
AU - St Clair, David
AU - Therman, Sebastian
AU - Toulopoulou, Timothea
AU - Van Os, Jim
AU - Waddington, John L.
AU - Sullivan, Patrick
AU - Vassos, Evangelos
AU - Breen, Gerome
AU - Collier, David Andrew
AU - Murray, Robin
AU - Schalkwyk, Leonard S.
AU - Mill, Jonathan
N1 - Publisher Copyright:
© 2021, eLife Sciences Publications Ltd. All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85101932123
U2 - 10.7554/eLife.58430
DO - 10.7554/eLife.58430
M3 - Article
C2 - 33646943
AN - SCOPUS:85101932123
SN - 2050-084X
VL - 10
SP - 1
EP - 53
JO - eLife
JF - eLife
M1 - e58430
ER -