| Zugriffsnummer | 49892 |
| Dokumenttyp | Zeitschriftenartikel |
| Peer Review | mit Peer Review |
| Sprache | Englisch |
| Titel | A causal association of ANKRD37 with human hippocampal volume |
| Autor(in); Institution |
Xu, J.; Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, CHINA
Xia, X.; Department of Cell Biology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, CHINA
Li, Q.; College of Information Engineering, Tianjin University of Commerce, Tianjin, CHINA
Dou, Y.; Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, CHINA
Suo, X.; Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, CHINA
Sun, Z.; Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, CHINA
Liu, N.; Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, CHINA
Han, Y.; Department of Pharmacology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammatory Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, CHINA
Sun, X.; Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, CHINA
He, Y.; Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, CHINA
Qin, W.; Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, CHINA
Zhang, S.; Department of Pharmacology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammatory Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, CHINA
Banaschewski, T.; Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, GERMANY
Flor, H.; Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, GERMANY
Grigis, A.; NeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, FRANCE
Gowland, P.; Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK
Heinz, A.; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, GERMANY
Martinot, J.-L.; Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale, INSERM “Developmental trajectories & psychiatry”; Ecole Normale supérieure Paris-Saclay, CNRS, Centre Borelli, Gif-sur-Yvette, FRANCE
Artiges, E.; Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale, “Developmental trajectories & psychiatry”, Ecole Normale supérieure Paris-Saclay, CNRS, Centre Borelli, Gif-sur-Yvette, and Etablissement Public de Santé (EPS) Barthélemy Durand, FRANCE
Nees, F.; Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, GERMANY
Paus, T.; Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital and Departments of Psychology and Psychiatry, University of Toronto, Toronto, CANADA
Poustka, L.; Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, GERMANY
Hohmann, S.; Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, GERMANY
Walter, H.; Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, GERMANY
Sham, P.; Centre for PanorOmic Sciences-Genomics and Bioinformatics Cores, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, CHINA
Schumann, G.; PONS Centre, Department of Psychiatry and Psychotherapy, CCM, Charite Universitaetsmedizin Berlin, Berlin, GERMANY
Wu, X.; Department of Cell Biology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, CHINA
Li, M.; Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, CHINA
Yu, C.; Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, CHINA
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| Quelle/Jahr | Molecular Psychiatry: 27 (2022), 4432 - 4445 |
| ISSN | 1359-4184 (print) ; 1476-5578 (online) |
| DOI | |
| Verlag | London: MacMillan |
| Zusammenfassung | Human hippocampal volume has been separately associated with single nucleotide polymorphisms (SNPs), DNA methylation and gene expression, but their causal relationships remain largely unknown. Here, we aimed at identifying the causal relationships of SNPs, DNA methylation, and gene expression that are associated with hippocampal volume by integrating cross-omics analyses with genome editing, overexpression and causality inference. Based on structural neuroimaging data and blood-derived genome, transcriptome and methylome data, we prioritized a possibly causal association across multiple molecular phenotypes: rs1053218 mutation leads to cg26741686 hypermethylation, thus leads to overactivation of the associated ANKRD37 gene expression in blood, a gene involving hypoxia, which may result in the reduction of human hippocampal volume. The possibly causal relationships from rs1053218 to cg26741686 methylation to ANKRD37 expression obtained from peripheral blood were replicated in human hippocampal tissue. To confirm causality, we performed CRISPR-based genome and epigenome-editing of rs1053218 homologous alleles and cg26741686 methylation in mouse neural stem cell differentiation models, and overexpressed ANKRD37 in mouse hippocampus. These in-vitro and in-vivo experiments confirmed that rs1053218 mutation caused cg26741686 hypermethylation and ANKRD37 overexpression, and cg26741686 hypermethylation favored ANKRD37 overexpression, and ANKRD37 overexpression reduced hippocampal volume. The pairwise relationships of rs1053218 with hippocampal volume, rs1053218 with cg26741686 methylation, cg26741686 methylation with ANKRD37 expression, and ANKRD37 expression with hippocampal volume could be replicated in an independent healthy young (n = 443) dataset and observed in elderly people (n = 194), and were more significant in patients with late-onset Alzheimer’s disease (n = 76). This study revealed a novel causal molecular association mechanism of ANKRD37 with human hippocampal volume, which may facilitate the design of prevention and treatment strategies for hippocampal impairment. |
| Themenbereich der Metrologie | Metrologie in der Medizin |
Zitierung
Xu, J., Xia, X., Li, Q., Dou, Y., Suo, X., Sun, Z., Liu, N., Han, Y., Sun, X., He, Y., Qin, W., Zhang, S., Banaschewski, T., Flor, H., Grigis, A., Gowland, P., Heinz, A., Brühl, R., Martinot, J.-L., Artiges, E., Nees, F., Paus, T., Poustka, L., Hohmann, S., Walter, H., Sham, P., Schumann, G., Wu, X., Li, M., & Yu, C. (2022). A causal association of ANKRD37 with human hippocampal volume. Molecular Psychiatry, 27, 4432–4445. https://doi.org/10.1038/s41380-022-01800-7