The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity
Abstract 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 relevan...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-07-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02548-6 |
| _version_ | 1797773969261068288 |
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| author | Svenja Müller Maurizio Sicorello Dirk Moser Leonard Frach Alicia Limberg Anja M. Gumpp Laura Ramo-Fernandez Franziska Köhler-Dauner Jörg M. Fegert Christiane Waller Robert Kumsta Iris-Tatjana Kolassa |
| author_facet | Svenja Müller Maurizio Sicorello Dirk Moser Leonard Frach Alicia Limberg Anja M. Gumpp Laura Ramo-Fernandez Franziska Köhler-Dauner Jörg M. Fegert Christiane Waller Robert Kumsta Iris-Tatjana Kolassa |
| author_sort | Svenja Müller |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T22:13:09Z |
| format | Article |
| id | doaj.art-a5a9eac482e545b3936c79fb17201ad9 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-12T22:13:09Z |
| publishDate | 2023-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-a5a9eac482e545b3936c79fb17201ad92023-07-23T11:27:13ZengNature Publishing GroupTranslational Psychiatry2158-31882023-07-011311910.1038/s41398-023-02548-6The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversitySvenja Müller0Maurizio Sicorello1Dirk Moser2Leonard Frach3Alicia Limberg4Anja M. Gumpp5Laura Ramo-Fernandez6Franziska Köhler-Dauner7Jörg M. Fegert8Christiane Waller9Robert Kumsta10Iris-Tatjana Kolassa11Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Genetic Psychology, Faculty of Psychology, Ruhr Universität BochumDepartment of Clinical, Educational and Health Psychology, Division of Psychology and Language Sciences, University College LondonDepartment of Genetic Psychology, Faculty of Psychology, Ruhr Universität BochumDepartment of Clinical & Biological Psychology, Institute of Psychology and Education, Ulm UniversityDepartment of Clinical & Biological Psychology, Institute of Psychology and Education, Ulm UniversityDepartment of Child and Adolescent Psychiatry/Psychotherapy, University Hospital UlmDepartment of Child and Adolescent Psychiatry/Psychotherapy, University Hospital UlmDepartment of Psychosomatic Medicine and Psychotherapy, University Hospital UlmDepartment of Genetic Psychology, Faculty of Psychology, Ruhr Universität BochumDepartment of Clinical & Biological Psychology, Institute of Psychology and Education, Ulm UniversityAbstract 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.https://doi.org/10.1038/s41398-023-02548-6 |
| spellingShingle | Svenja Müller Maurizio Sicorello Dirk Moser Leonard Frach Alicia Limberg Anja M. Gumpp Laura Ramo-Fernandez Franziska Köhler-Dauner Jörg M. Fegert Christiane Waller Robert Kumsta Iris-Tatjana Kolassa The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity Translational Psychiatry |
| 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 |
| url | https://doi.org/10.1038/s41398-023-02548-6 |
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