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

Emma L. Dempster; Chloe C.Y. Wong; Joe Burrage; Eilis Hannon; Diego Quattrone; Giulia Trotta; Victoria Rodriguez; Luis Alameda; Edoardo Spinazzola; Giada Tripoli; Isabelle Austin-Zimmerman; Zhikun Li; Charlotte Gayer-Anderson; Tom P. Freeman; Emma C. Johnson; Hannah E. Jongsma; Simona Stilo; Caterina La Cascia; Laura Ferraro; Daniele La Barbera; Antonio Lasalvia; Sarah Tosato; Ilaria Tarricone; Giuseppe D’Andrea; Michela Galatolo; Andrea Tortelli; Maurizio Pompili; Jean Paul Selten; Lieuwe de Haan; Paulo Rossi Menezes; Cristina M. Del Ben; Jose Luis Santos; Manuel Arrojo; Julio Bobes; Julio Sanjuán; Miguel Bernardo; Celso Arango; Peter B. Jones; Gerome Breen; Valeria Mondelli; Paola Dazzan; Conrad Iyegbe; Evangelos Vassos; Craig Morgan; Diptendu Mukherjee; Jim van Os; Bart Rutten; Michael C. O’Donovan; Pak Sham; Jonathan Mill; Robin Murray; Marta Di Forti

doi:10.1038/s41380-024-02689-0

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

Emma L. Dempster^*, Chloe C.Y. Wong, Joe Burrage, Eilis Hannon, Diego Quattrone, Giulia Trotta, Victoria Rodriguez, Luis Alameda, Edoardo Spinazzola, Giada Tripoli, Isabelle Austin-Zimmerman, Zhikun Li, Charlotte Gayer-Anderson, Tom P. Freeman, Emma C. Johnson, Hannah E. Jongsma, Simona Stilo, Caterina La Cascia, Laura Ferraro, Daniele La BarberaAntonio Lasalvia, Sarah Tosato, Ilaria Tarricone, Giuseppe D’Andrea, Michela Galatolo, Andrea Tortelli, Maurizio Pompili, Jean Paul Selten, Lieuwe de Haan, Paulo Rossi Menezes, Cristina M. Del Ben, Jose Luis Santos, Manuel Arrojo, Julio Bobes, Julio Sanjuán, Miguel Bernardo, Celso Arango, Peter B. Jones, Gerome Breen, Valeria Mondelli, Paola Dazzan, Conrad Iyegbe, Evangelos Vassos, Craig Morgan, Diptendu Mukherjee, Jim van Os, Bart Rutten, Michael C. O’Donovan, Pak Sham, Jonathan Mill, Robin Murray, Marta Di Forti

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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 = &#x003E; 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.

Original language	English
Journal	Molecular Psychiatry
DOIs	https://doi.org/10.1038/s41380-024-02689-0
Publication status	Accepted/In press - 2024

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Dempster, E. L., Wong, C. C. Y., Burrage, J., Hannon, E., Quattrone, D., Trotta, G., Rodriguez, V., Alameda, L., Spinazzola, E., Tripoli, G., Austin-Zimmerman, I., Li, Z., Gayer-Anderson, C., Freeman, T. P., Johnson, E. C., Jongsma, H. E., Stilo, S., La Cascia, C., Ferraro, L., ... Di Forti, M. (Accepted/In press). Methylomic signature of current cannabis use in two first-episode psychosis cohorts. Molecular Psychiatry. https://doi.org/10.1038/s41380-024-02689-0

@article{f1e26d553bbc4bac88e7ac795eccdb30,

title = "Methylomic signature of current cannabis use in two first-episode psychosis cohorts",

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.",

author = "Dempster, {Emma L.} and Wong, {Chloe C.Y.} and Joe Burrage and Eilis Hannon and Diego Quattrone and Giulia Trotta and Victoria Rodriguez and Luis Alameda and Edoardo Spinazzola and Giada Tripoli and Isabelle Austin-Zimmerman and Zhikun Li and Charlotte Gayer-Anderson and Freeman, {Tom P.} and Johnson, {Emma C.} and Jongsma, {Hannah E.} and Simona Stilo and {La Cascia}, Caterina and Laura Ferraro and {La Barbera}, Daniele and Antonio Lasalvia and Sarah Tosato and Ilaria Tarricone and Giuseppe D{\textquoteright}Andrea and Michela Galatolo and Andrea Tortelli and Maurizio Pompili and Selten, {Jean Paul} and {de Haan}, Lieuwe and Menezes, {Paulo Rossi} and {Del Ben}, {Cristina M.} and Santos, {Jose Luis} and Manuel Arrojo and Julio Bobes and Julio Sanju{\'a}n and Miguel Bernardo and Celso Arango and Jones, {Peter B.} and Gerome Breen and Valeria Mondelli and Paola Dazzan and Conrad Iyegbe and Evangelos Vassos and Craig Morgan and Diptendu Mukherjee and {van Os}, Jim and Bart Rutten and O{\textquoteright}Donovan, {Michael C.} and Pak Sham and Jonathan Mill and Robin Murray and {Di Forti}, Marta",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

doi = "10.1038/s41380-024-02689-0",

language = "English",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Springer Nature [academic journals on nature.com]",

}

Dempster, EL, Wong, CCY, Burrage, J, Hannon, E, Quattrone, D, Trotta, G, Rodriguez, V, Alameda, L, Spinazzola, E, Tripoli, G, Austin-Zimmerman, I, Li, Z, Gayer-Anderson, C , Freeman, TP, Johnson, EC, Jongsma, HE, Stilo, S, La Cascia, C, Ferraro, L, La Barbera, D, Lasalvia, A, Tosato, S, Tarricone, I, D’Andrea, G, Galatolo, M, Tortelli, A, Pompili, M, Selten, JP, de Haan, L, Menezes, PR, Del Ben, CM, Santos, JL, Arrojo, M, Bobes, J, Sanjuán, J, Bernardo, M, Arango, C, Jones, PB, Breen, G, Mondelli, V , Dazzan, P , Iyegbe, C , Vassos, E , Morgan, C, Mukherjee, D, van Os, J, Rutten, B, O’Donovan, MC, Sham, P, Mill, J, Murray, R & Di Forti, M 2024, 'Methylomic signature of current cannabis use in two first-episode psychosis cohorts', Molecular Psychiatry. https://doi.org/10.1038/s41380-024-02689-0

TY - JOUR

T1 - Methylomic signature of current cannabis use in two first-episode psychosis cohorts

AU - Dempster, Emma L.

AU - Wong, Chloe C.Y.

AU - Burrage, Joe

AU - Hannon, Eilis

AU - Quattrone, Diego

AU - Trotta, Giulia

AU - Rodriguez, Victoria

AU - Alameda, Luis

AU - Spinazzola, Edoardo

AU - Tripoli, Giada

AU - Austin-Zimmerman, Isabelle

AU - Li, Zhikun

AU - Gayer-Anderson, Charlotte

AU - Freeman, Tom P.

AU - Johnson, Emma C.

AU - Jongsma, Hannah E.

AU - Stilo, Simona

AU - La Cascia, Caterina

AU - Ferraro, Laura

AU - La Barbera, Daniele

AU - Lasalvia, Antonio

AU - Tosato, Sarah

AU - Tarricone, Ilaria

AU - D’Andrea, Giuseppe

AU - Galatolo, Michela

AU - Tortelli, Andrea

AU - Pompili, Maurizio

AU - Selten, Jean Paul

AU - de Haan, Lieuwe

AU - Menezes, Paulo Rossi

AU - Del Ben, Cristina M.

AU - Santos, Jose Luis

AU - Arrojo, Manuel

AU - Bobes, Julio

AU - Sanjuán, Julio

AU - Bernardo, Miguel

AU - Arango, Celso

AU - Jones, Peter B.

AU - Breen, Gerome

AU - Mondelli, Valeria

AU - Dazzan, Paola

AU - Iyegbe, Conrad

AU - Vassos, Evangelos

AU - Morgan, Craig

AU - Mukherjee, Diptendu

AU - van Os, Jim

AU - Rutten, Bart

AU - O’Donovan, Michael C.

AU - Sham, Pak

AU - Mill, Jonathan

AU - Murray, Robin

AU - Di Forti, Marta

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85206916435&partnerID=8YFLogxK

U2 - 10.1038/s41380-024-02689-0

DO - 10.1038/s41380-024-02689-0

M3 - Article

C2 - 39406996

AN - SCOPUS:85206916435

SN - 1359-4184

JO - Molecular Psychiatry

JF - Molecular Psychiatry

ER -

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

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