Exploring the mediation of DNA methylation across the epigenome between childhood adversity and First Episode of Psychosis-findings from the EU-GEI study

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2
Tipo de produção
article
Data de publicação
2023
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Scopus
Web of Science
PubMed
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SPRINGERNATURE
Autores
ALAMEDA, Luis
LIU, Zhonghua
SHAM, Pak C.
AAS, Monica
TROTTA, Giulia
RODRIGUEZ, Victoria
FORTI, Marta Di
STILO, Simona A.
KANDASWAMY, Radhika
ARANGO, Celso
Citação
MOLECULAR PSYCHIATRY, v.28, n.5, p.2095-2106, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
AbtractStudies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue from 366 First-episode of psychosis and 517 healthy controls was performed. Adversity scores were created for abuse, neglect and composite adversity with the Childhood Trauma Questionnaire (CTQ). Regressions examining (I) CTQ scores with psychosis; (II) with DNAm EWAS level and (III) between DNAm and caseness, adjusted for a variety of confounders were conducted. Divide-Aggregate Composite-null Test for the composite null-hypothesis of no mediation effect was conducted. Enrichment analyses were conducted with missMethyl package and the KEGG database. Our results show that CA was associated with psychosis (Composite: OR = 1.68; p = p < 0.001; neglect: OR = 2.27; p = <0.001). None of the CpG sites significantly mediated the adversity-psychosis association after Bonferroni correction (p < 8.1 x 10(-8)). However, 28, 34 and 29 differentially methylated probes associated with 21, 27, 20 genes passed a less stringent discovery threshold (p < 5 x 10(-5)) for composite, abuse and neglect respectively, with a lack of overlap between abuse and neglect. These included genes previously associated to psychosis in EWAS studies, such as PANK1, SPEG TBKBP1, TSNARE1 or H2R. Downstream gene ontology analyses did not reveal any biological pathways that survived false discovery rate correction. Although at a non-significant level, DNAm changes in genes previously associated with schizophrenia in EWAS studies may mediate the CA-psychosis association. These results and associated involved processes such as mitochondrial or histaminergic disfunction, immunity or neural signalling requires replication in well powered samples. The lack of overlap between mediating genes associated with abuse and neglect suggests differential biological trajectories linking CA subtypes and psychosis.
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https://observatorio.fm.usp.br/handle/OPI/57506
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPR
Artigos e Materiais de Revistas Científicas - LIM/39
Artigos e Materiais de Revistas Científicas - ODS/16