DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia.
Elife
; 102021 02 26.
Article
en En
| MEDLINE
| ID: mdl-33646943
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trastornos Psicóticos
/
Metilación de ADN
/
Epigenoma
/
Esquizofrenia Resistente al Tratamiento
Tipo de estudio:
Prognostic_studies
/
Systematic_reviews
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Elife
Año:
2021
Tipo del documento:
Article
País de afiliación:
Reino Unido