Methylomic signature of current cannabis use in two first-episode psychosis cohorts

Dempster, Emma, Wong, Chloe, Burrage, Joe, Hannon, Eilis, Quattrone, Diego, Trotta, Giulia, Rodriguez, Victoria, Alameda, Luis, Spinazzola, Edouardo, Tripoli, Giada, Austin-Zimmerman, Isabelle, Li, Zhikun, Gayer-Anderson, Charlotte, Freeman, Tom, Johnson, Emma, Jongsma, Hannah, Stilo, Simona, La Cascia, Caterina, Ferraro, Laura, La Barbera, Daniele, Lasalvia, Antonio, Tosato, Sarah, Tarricone, Ilaria, D'Andrea, Giuseppe, Galatolo, Michela, Tortelli, Andrea, Pompili, Maurizio, Selten, Jean-Paul, de Haan, Lieuwe, Rossi Menezes, Paulo, Del Ben, Cristina M, Santos, Jose Luis, Arrojo, Manuel, Bobes, Julio, Sanjuan, Miguel, Arango, Celso, Jones, Peter B, Breen, Gerome, Mondelli, Valeria, Dazzan, Paola, Iyegbe, Conrad, Vassos, Evangelos, Morgan, Craig, Mukherjee, Diptendu, van Os, Jim, Rutten, Bart, O'Donovan, Michael ORCID: https://orcid.org/0000-0001-7073-2379, Sham, Pak, Mill, Jonathan, Murray, Robin and Di Forti, Marta 2024. Methylomic signature of current cannabis use in two first-episode psychosis cohorts. Molecular Psychiatry 10.1038/s41380-024-02689-0

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Abstract

The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples using the Illumina DNA methylation array platform. A meta-analysis across cohorts identified one CpG site (cg11669285) in the CAVIN1 gene that showed differential methylation with current cannabis use, surpassing the array-wide significance threshold, and independent of the tobacco-related epigenetic signature. Furthermore, a CpG site localised in the MCU gene (cg11669285) achieved array-wide significance in an analysis of the effect of high-potency (THC = > 10%) current cannabis use. Pathway and regional analyses identified cannabis-related epigenetic variation proximal to genes linked to immune and mitochondrial function, both of which are known to be influenced by cannabinoids. Interestingly, a model including an interaction term between cannabis use and FEP status identified two sites that were significantly associated with current cannabis use with a nominally significant interaction suggesting that FEP status might moderate how cannabis use affects DNA methylation. Overall, these findings contribute to our understanding of the epigenetic impact of current cannabis use and highlight potential molecular pathways affected by cannabis exposure.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher:	Springer Nature
ISSN:	1359-4184
Date of First Compliant Deposit:	25 July 2024
Date of Acceptance:	31 July 2024
Last Modified:	21 Oct 2024 13:35
URI:	https://orca.cardiff.ac.uk/id/eprint/170928

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