DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia
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- Eilis Hannon
- University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, United Kingdom
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- Emma L Dempster
- University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, United Kingdom
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- Georgina Mansell
- University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, United Kingdom
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- Joe Burrage
- University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, United Kingdom
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- Nick Bass
- Division of Psychiatry, University College London, London, United Kingdom
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- Marc M Bohlken
- Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan, Utrecht, Netherlands
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- Aiden Corvin
- Department of Psychiatry and Neuropsychiatric Genetics Research Group, Trinity Translational Medicine Institute, Trinity College Dublin, St. James Hospital, Dublin, Ireland
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- Charles J Curtis
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
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- David Dempster
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
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- Marta Di Forti
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
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- Timothy G Dinan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
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- Gary Donohoe
- Centre for Neuroimaging and Cognitive Genomics (NICOG), School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland
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- Fiona Gaughran
- Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
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- Michael Gill
- Department of Psychiatry and Neuropsychiatric Genetics Research Group, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
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- Amy Gillespie
- Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
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- Cerisse Gunasinghe
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
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- Hilleke E Hulshoff
- Department of Psychiatry, University Medical Center Utrecht, Utrecht, Netherlands
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- Christina M Hultman
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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- Viktoria Johansson
- Department of Medical Epidemiology and Biostatistics Sweden, Karolinska Institutet, Stockholm, Sweden
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- René S Kahn
- Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands
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- Jaakko Kaprio
- Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland
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- Gunter Kenis
- Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
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- Kaarina Kowalec
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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- James MacCabe
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
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- Colm McDonald
- Centre for Neuroimaging and Cognitive Genomics (NICOG), School of Medicine, National University of Ireland Galway, Galway, Ireland
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- Andrew McQuillin
- Division of Psychiatry, University College London, London, United Kingdom
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- Derek W Morris
- Centre for Neuroimaging and Cognitive Genomics (NICOG), School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland
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- Kieran C Murphy
- Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland
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- Colette J Mustard
- Division of Biomedical Sciences, Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, United Kingdom
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- Igor Nenadic
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
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- Michael C O'Donovan
- MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom
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- Diego Quattrone
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
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- Alexander L Richards
- MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom
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- Bart PF Rutten
- Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
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- David St Clair
- The Institute of Medical Sciences, Univeristy of Aberdeen, Aberdeen, United Kingdom
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- Sebastian Therman
- Department of Public Health Solutions, Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland
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- Timothea Toulopoulou
- Department of Psychology and National Magnetic Resonance Research Center (UMRAM), Aysel Sabuncu Brain Research Centre (ASBAM), Bilkent University, Ankara, Turkey
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- Jim Van Os
- Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands
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- John L Waddington
- Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
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- Patrick Sullivan
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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- Evangelos Vassos
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
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- Gerome Breen
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
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- David Andrew Collier
- Neuroscience Genetics, Eli Lilly and Company, Surrey, United Kingdom
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- Robin M Murray
- Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, United Kingdom
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- Leonard S Schalkwyk
- School of Life Sciences, University of Essex, Colchester, United Kingdom
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- Jonathan Mill
- University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, United Kingdom
説明
<jats:p>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.</jats:p>
収録刊行物
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- eLife
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eLife 10 e58430-, 2021-02-26
eLife Sciences Publications, Ltd
