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The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity

The oxytocin receptor gene (OXTR) is of interest when investigating the effects of early adversity on DNA methylation. However, there is heterogeneity regarding the selection of the most promising CpG sites to target for analyses. The goal of this study was to determine functionally relevant cluster...

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Autores principales: Müller, Svenja, Sicorello, Maurizio, Moser, Dirk, Frach, Leonard, Limberg, Alicia, Gumpp, Anja M., Ramo-Fernandez, Laura, Köhler-Dauner, Franziska, Fegert, Jörg M., Waller, Christiane, Kumsta, Robert, Kolassa, Iris-Tatjana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362059/
https://www.ncbi.nlm.nih.gov/pubmed/37479681
http://dx.doi.org/10.1038/s41398-023-02548-6
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author Müller, Svenja
Sicorello, Maurizio
Moser, Dirk
Frach, Leonard
Limberg, Alicia
Gumpp, Anja M.
Ramo-Fernandez, Laura
Köhler-Dauner, Franziska
Fegert, Jörg M.
Waller, Christiane
Kumsta, Robert
Kolassa, Iris-Tatjana
author_facet Müller, Svenja
Sicorello, Maurizio
Moser, Dirk
Frach, Leonard
Limberg, Alicia
Gumpp, Anja M.
Ramo-Fernandez, Laura
Köhler-Dauner, Franziska
Fegert, Jörg M.
Waller, Christiane
Kumsta, Robert
Kolassa, Iris-Tatjana
author_sort Müller, Svenja
collection PubMed
description The oxytocin receptor gene (OXTR) is of interest when investigating the effects of early adversity on DNA methylation. However, there is heterogeneity regarding the selection of the most promising CpG sites to target for analyses. The goal of this study was to determine functionally relevant clusters of CpG sites within the OXTR CpG island in 113 mother-infant dyads, with 58 of the mothers reporting childhood maltreatment (CM). OXTR DNA methylation was analyzed in peripheral/umbilical blood mononuclear cells. Different complexity reduction approaches were used to reduce the 188 CpG sites into clusters of co-methylated sites. Furthermore, associations between OXTR DNA methylation (cluster- and site-specific level) and OXTR gene expression and CM were investigated in mothers. Results showed that, first, CpG sections differed strongly regarding their statistical utility for research of individual differences in DNA methylation. Second, cluster analyses and Partial Least Squares (PLS) suggested two clusters consisting of intron1/exon2 and the protein-coding region of exon3, respectively, as most strongly associated with outcome measures. Third, cross-validated PLS regression explained 7% of variance in CM, with low cross-validated variance explained for the prediction of gene expression. Fourth, substantial mother-child correspondence was observed in correlation patterns within the identified clusters, but only modest correspondence outside these clusters. This study makes an important contribution to the mapping of the DNA methylation landscape of the OXTR CpG island by highlighting clusters of CpG sites that show desirable statistical properties and predictive value. We provide a Companion Web Application to facilitate the choice of CpG sites.
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spelling pubmed-103620592023-07-23 The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity Müller, Svenja Sicorello, Maurizio Moser, Dirk Frach, Leonard Limberg, Alicia Gumpp, Anja M. Ramo-Fernandez, Laura Köhler-Dauner, Franziska Fegert, Jörg M. Waller, Christiane Kumsta, Robert Kolassa, Iris-Tatjana Transl Psychiatry Article The oxytocin receptor gene (OXTR) is of interest when investigating the effects of early adversity on DNA methylation. However, there is heterogeneity regarding the selection of the most promising CpG sites to target for analyses. The goal of this study was to determine functionally relevant clusters of CpG sites within the OXTR CpG island in 113 mother-infant dyads, with 58 of the mothers reporting childhood maltreatment (CM). OXTR DNA methylation was analyzed in peripheral/umbilical blood mononuclear cells. Different complexity reduction approaches were used to reduce the 188 CpG sites into clusters of co-methylated sites. Furthermore, associations between OXTR DNA methylation (cluster- and site-specific level) and OXTR gene expression and CM were investigated in mothers. Results showed that, first, CpG sections differed strongly regarding their statistical utility for research of individual differences in DNA methylation. Second, cluster analyses and Partial Least Squares (PLS) suggested two clusters consisting of intron1/exon2 and the protein-coding region of exon3, respectively, as most strongly associated with outcome measures. Third, cross-validated PLS regression explained 7% of variance in CM, with low cross-validated variance explained for the prediction of gene expression. Fourth, substantial mother-child correspondence was observed in correlation patterns within the identified clusters, but only modest correspondence outside these clusters. This study makes an important contribution to the mapping of the DNA methylation landscape of the OXTR CpG island by highlighting clusters of CpG sites that show desirable statistical properties and predictive value. We provide a Companion Web Application to facilitate the choice of CpG sites. Nature Publishing Group UK 2023-07-21 /pmc/articles/PMC10362059/ /pubmed/37479681 http://dx.doi.org/10.1038/s41398-023-02548-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Müller, Svenja
Sicorello, Maurizio
Moser, Dirk
Frach, Leonard
Limberg, Alicia
Gumpp, Anja M.
Ramo-Fernandez, Laura
Köhler-Dauner, Franziska
Fegert, Jörg M.
Waller, Christiane
Kumsta, Robert
Kolassa, Iris-Tatjana
The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity
title The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity
title_full The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity
title_fullStr The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity
title_full_unstemmed The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity
title_short The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity
title_sort dna methylation landscape of the human oxytocin receptor gene (oxtr): data-driven clusters and their relation to gene expression and childhood adversity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362059/
https://www.ncbi.nlm.nih.gov/pubmed/37479681
http://dx.doi.org/10.1038/s41398-023-02548-6
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