| Zugriffsnummer | 43214 |
| Dokumenttyp | Zeitschriftenartikel |
| Peer Review | mit Peer Review |
| Sprache | Englisch |
| Titel | Association of a Schizophrenia-risk nonsynonymous variant with putamen volume in adolescents: A voxelwise and genome-wide association study |
| Autor(in); Institution |
Luo, Q.; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, CHINA
Chen, Q.; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA
Wang, W.; Pharnext, Issy-les-Moulineaux, Ile de France, FRANCE
Desrivières, S.; Centre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Social Genetic and Developmental Psychiatry Centre, London, UK
Quinlan, E.; Centre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Social Genetic and Developmental Psychiatry Centre, London, UK
Jia, T.; Centre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Social Genetic and Developmental Psychiatry Centre, London, UK
Macare, C.; Centre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Social Genetic and Developmental Psychiatry Centre, London, UK
Robert, G.; EA 4712 "Behavior and Basal Ganglia," Rennes University, Rennes, FRANCE
Cui, J.; Laboratory for Research in Neuroimaging, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, SWITZERLAND
Guedj, M.; Pharnext, Issy-les-Moulineaux, Ile de France, FRANCE
Palaniyappan, L.; Departments of Psychiatry and Medical Biophysics, Robarts Research Institute, University of Western Ontario, London, Ontario, CANADA
Kherif, F.; Laboratory for Research in Neuroimaging, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, SWITZERLAND
Banaschewski, T.; Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, GERMANY
Bokde, A.; Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, IRELAND
Büchel, C.; University Medical Centre Hamburg-Eppendorf, Hamburg, GERMANY
Flor, H.; Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, GERMANY
Frouin, V.; NeuroSpin, Commissariat à L'énergie Atomique, Université Paris-Saclay, Gif-sur-Yvette, FRANCE
Garavan, H.; Departments of Psychiatry and Psychology, University of Vermont, Burlington, USA
Gowland, P.; Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK
Heinz, A.; Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, GERMANY
Ittermann, Bernd; 8.1, Biomedizinische Magnetresonanz, PTB-Berlin
Martinot, J.; Institut National de la Santé et de la Recherche Médicale Unit 1000, Neuroimaging and Psychiatry, University Paris Sud-Paris Saclay, University Paris Descartes, Paris, FRANCE
Artiges, E.; Institut National de la Santé et de la Recherche Médicale Unit 1000, Neuroimaging and Psychiatry, University Paris Sud-Paris Saclay, University Paris Descartes, Paris, FRANCE
Paillère-Martinot, M.; Institut National de la Santé et de la Recherche Médicale Unit 1000, Neuroimaging and Psychiatry, University Paris Sud-Paris Saclay, University Paris Descartes, Paris, FRANCE
Nees, F.; Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, GERMANY
Orfanos, D.; NeuroSpin, Commissariat à L'énergie Atomique, Université Paris-Saclay, Gif-sur-Yvette, FRANCE
Poustka, L.; Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, Göttingen, GERMANY
Fröhner, J.; Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, GERMANY
Smolka, M.; Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, GERMANY
Walter, H.; Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, GERMANY
Whelan, R.; School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, IRELAND
Callicott, J.; Clinical and Translational Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
Mattay, V.; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Pausova, Z.; The Hospital for Sick Children, University of Toronto, Toronto, Ontario, CANADA
Dartigues, J.; Institut National de la Santé et de la Recherche Médicale Unit 1219, Université de Bordeaux, Bordeaux, FRANCE
Tzourio, C.; Institut National de la Santé et de la Recherche Médicale Unit 1219, Université de Bordeaux, Bordeaux, FRANCE
Crivello, F.; University de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, FRANCE
Berman, K.; Clinical and Translational Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
Li, F.; Developmental and Behavioral Pediatric Department and Child Primary Care Department, MOE-Shanghai Key Lab for Children's Environmental Health, Xinhua Hospital Affiliated To Shang Jiaotong University School of Medicine, Shanghai, CHINA
Paus, T.; Departments of Psychology and Psychiatry, University of Toronto, Toronto, Ontario, CANADA
Weinberger, D.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
Murray, R.; Centre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Social Genetic and Developmental Psychiatry Centre, London, UK
Schumann, G.; Centre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Social Genetic and Developmental Psychiatry Centre, London, UK
Feng, J.; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, CHINA
IMAGEN consortium,
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| Quelle/Jahr | JAMA Psychiatry: 76 (2019), 4, 435 - 445 |
| ISSN | 2168-622X (PRINT) ; 2168-6238 (ONLINE) |
| DOI | |
| Verlag | Chicago, Ill.: American Medical Association (AMA) |
| Zusammenfassung | Importance: Deviation from normal adolescent brain development precedes manifestations of many major psychiatric symptoms. Such altered developmental trajectories in adolescents may be linked to genetic risk for psychopathology. Objective: To identify genetic variants associated with adolescent brain structure and explore psychopathologic relevance of such associations. Design, Setting, and Participants: Voxelwise genome-wide association study in a cohort of healthy adolescents aged 14 years and validation of the findings using 4 independent samples across the life span with allele-specific expression analysis of top hits. Group comparison of the identified gene-brain association among patients with schizophrenia, unaffected siblings, and healthy control individuals. This was a population-based, multicenter study combined with a clinical sample that included participants from the IMAGEN cohort, Saguenay Youth Study, Three-City Study, and Lieber Institute for Brain Development sample cohorts and UK biobank who were assessed for both brain imaging and genetic sequencing. Clinical samples included patients with schizophrenia and unaffected siblings of patients from the Lieber Institute for Brain Development study. Data were analyzed between October 2015 and April 2018. Main Outcomes and Measures: Gray matter volume was assessed by neuroimaging and genetic variants were genotyped by Illumina BeadChip. Results: The discovery sample included 1721 adolescents (873 girls [50.7%]), with a mean (SD) age of 14.44 (0.41) years. The replication samples consisted of 8690 healthy adults (4497 women [51.8%]) from 4 independent studies across the life span. A nonsynonymous genetic variant (minor T allele of rs13107325 in SLC39A8, a gene implicated in schizophrenia) was associated with greater gray matter volume of the putamen (variance explained of 4.21% in the left hemisphere; 8.66; 95% CI, 6.59-10.81; P = 5.35 × 10-18; and 4.44% in the right hemisphere; t = 8.90; 95% CI, 6.75-11.19; P = 6.80 × 10-19) and also with a lower gene expression of SLC39A8 specifically in the putamen (t127 = -3.87; P = 1.70 × 10-4). The identified association was validated in samples across the life span but was significantly weakened in both patients with schizophrenia (z = -3.05; P = .002; n = 157) and unaffected siblings (z = -2.08; P = .04; n = 149). Conclusions and Relevance: Our results show that a missense mutation in gene SLC39A8 is associated with larger gray matter volume in the putamen and that this association is significantly weakened in schizophrenia. These results may suggest a role for aberrant ion transport in the etiology of psychosis and provide a target for preemptive developmental interventions aimed at restoring the functional effect of this mutation. |
| Kostenfreier Zugang | Open Access Hybrid |
| Rechteinformation | CC BY 4.0 ; Creative Commons Attribution 4.0 License |
| Themenbereich der Metrologie | Metrologie in der Medizin |
Zitierung
Luo, Q., Chen, Q., Wang, W., Desrivières, S., Quinlan, E., Jia, T., Macare, C., Robert, G., Cui, J., Guedj, M., Palaniyappan, L., Kherif, F., Banaschewski, T., Bokde, A., Büchel, C., Flor, H., Frouin, V., Garavan, H., Gowland, P., Heinz, A., Ittermann, B., Martinot, J., Artiges, E., Paillère-Martinot, M., Nees, F., Orfanos, D., Poustka, L., Fröhner, J., Smolka, M., Walter, H., Whelan, R., Callicott, J., Mattay, V., Pausova, Z., Dartigues, J., Tzourio, C., Crivello, F., Berman, K., Li, F., Paus, T., Weinberger, D., Murray, R., Schumann, G., Feng, J., & IMAGEN consortium. (2019). Association of a Schizophrenia-risk nonsynonymous variant with putamen volume in adolescents: A voxelwise and genome-wide association study. JAMA Psychiatry, 76(4), 435–445. https://doi.org/10.1001/jamapsychiatry.2018.4126