Potentially causal associations between placental DNA methylation and schizophrenia and other neuropsychiatric disorders

Ariadna Cilleros-Portet, Corina Lesseur, Sergi Marí, Marta Cosin-Tomas, Manuel Lozano, Amaia Irizar, Amber Burt, Iraia García-Santisteban, Diego Garrido-Martín, Geòrgia Escaramís, Alba Hernangomez-Laderas, Raquel Soler-Blasco, Charles E. Breeze, Bárbara P. Gonzalez-Garcia, Loreto Santa-Marina, Jia Chen, Sabrina Llop, Mariana F. Fernández, Martine Vrijheid, Jesús Ibarluzea, Mònica Guxens, Carmen Marsit, Mariona Bustamante, Jose Ramon Bilbao and Nora Fernandez-Jimenez ()
Additional contact information
Ariadna Cilleros-Portet: Biobizkaia Health Research Institute and University of the Basque Country (UPV/EHU)
Corina Lesseur: Icahn School of Medicine at Mount Sinai
Sergi Marí: Biobizkaia Health Research Institute and University of the Basque Country (UPV/EHU)
Marta Cosin-Tomas: ISGlobal
Manuel Lozano: FISABIO-Universitat Jaume I-Universitat de València
Amaia Irizar: Instituto de Salud Carlos III
Amber Burt: Emory University
Iraia García-Santisteban: Biobizkaia Health Research Institute and University of the Basque Country (UPV/EHU)
Diego Garrido-Martín: Universitat de Barcelona (UB)
Geòrgia Escaramís: Instituto de Salud Carlos III
Alba Hernangomez-Laderas: Biobizkaia Health Research Institute and University of the Basque Country (UPV/EHU)
Raquel Soler-Blasco: Instituto de Salud Carlos III
Charles E. Breeze: University College London
Bárbara P. Gonzalez-Garcia: Biobizkaia Health Research Institute and University of the Basque Country (UPV/EHU)
Loreto Santa-Marina: Instituto de Salud Carlos III
Jia Chen: Icahn School of Medicine at Mount Sinai
Sabrina Llop: Instituto de Salud Carlos III
Mariana F. Fernández: Instituto de Salud Carlos III
Martine Vrijheid: ISGlobal
Jesús Ibarluzea: Instituto de Salud Carlos III
Mònica Guxens: ISGlobal
Carmen Marsit: Emory University
Mariona Bustamante: ISGlobal
Jose Ramon Bilbao: Biobizkaia Health Research Institute and University of the Basque Country (UPV/EHU)
Nora Fernandez-Jimenez: Biobizkaia Health Research Institute and University of the Basque Country (UPV/EHU)

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract Increasing evidence supports the role of the placenta in neurodevelopment and in the onset of neuropsychiatric disorders. Recently, mQTL and iQTL maps have proven useful in understanding relationships between SNPs and GWAS that are not captured by eQTL. In this context, we propose that part of the genetic predisposition to complex neuropsychiatric disorders acts through placental DNA methylation. We construct a public placental cis-mQTL database including 214,830 CpG sites calculated in 368 fetal placenta DNA samples from the INMA project, and run cell type-, gestational age- and sex-imQTL models. We combine these data with summary statistics of GWAS on ten neuropsychiatric disorders using summary-based Mendelian randomization and colocalization. We also evaluate the influence of identified DNA methylation sites on placental gene expression in the RICHS cohort. We find that placental cis-mQTLs are enriched in placenta-specific active chromatin regions, and establish that part of the genetic burden for schizophrenia, bipolar disorder, and major depressive disorder confers risk through placental DNA methylation. The potential causality of several of the observed associations is reinforced by secondary association signals identified in conditional analyses, the involvement of cell type-imQTLs, and the correlation of identified DNA methylation sites with the expression levels of relevant genes in the placenta.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57760-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57760-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-57760-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().