1. Maternally Derived Microduplications at 15q11-q13: Implication of Imprinted Genes in Psychotic Illness
- Author
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Ingason, Andrés, Kirov, George, Giegling, Ina, Hansen, Thomas, Isles, Anthony R., Jakobsen, Klaus D., Kristinsson, Kari T., le Roux, Louise, Gustafsson, Omar, Craddock, Nick, Möller, Hans-Jürgen, McQuillin, Andrew, Muglia, Pierandrea, Cichon, Sven, Rietschel, Marcella, Ophoff, Roel A., Djurovic, Srdjan, Andreassen, Ole A., Pietiläinen, Olli P. H., Peltonen, Leena, Dempster, Emma, Collier, David A., St Clair, David, Rasmussen, Henrik B., Glenthøj, Birte Y., Kiemeney, Lambertus A., Franke, Barbara, Tosato, Sarah, Bonetto, Chiara, Saemundsen, Evald, Hreidarsson, Stefán J., Nöthen, Markus M., Gurling, Hugh, O'Donovan, Michael C., Owen, Michael J., Sigurdsson, Engilbert, Petursson, Hannes, Stefansson, Hreinn, Rujescu, Dan, Stefansson, Kari, Werge, Thomas, Linszen, Don, ANS - Amsterdam Neuroscience, Adult Psychiatry, Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience, and Research Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark.
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Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Genetics and epigenetic pathways of disease [NCMLS 6] ,Adolescent ,DNA Copy Number Variations ,Genotype ,Denmark ,Mothers ,Schizoaffective disorder ,Genomic disorders and inherited multi-system disorders Functional Neurogenomics [IGMD 3] ,Article ,Genomic disorders and inherited multi-system disorders [IGMD 3] ,Molecular epidemiology [NCEBP 1] ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Angelman syndrome ,Gene duplication ,medicine ,Humans ,Copy-number variation ,Age of Onset ,Child ,Genetic Association Studies ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,030304 developmental biology ,Psychiatry ,Genetics ,Chromosomes, Human, Pair 15 ,0303 health sciences ,Great Britain ,Uniparental Disomy ,medicine.disease ,United Kingdom ,Uniparental disomy ,3. Good health ,Blotting, Southern ,Psychiatry and Mental health ,Psychotic Disorders ,Schizophrenia ,Autism ,Female ,Age of onset ,Psychology ,Functional Neurogenomics [DCN 2] ,Prader-Willi Syndrome ,030217 neurology & neurosurgery - Abstract
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. OBJECTIVE: Rare copy number variants have been implicated in different neurodevelopmental disorders, with the same copy number variants often increasing risk of more than one of these phenotypes. In a discovery sample of 22 schizophrenia patients with an early onset of illness (10-15 years of age), the authors observed in one patient a maternally derived 15q11-q13 duplication overlapping the Prader-Willi/Angelman syndrome critical region. This prompted investigation of the role of 15q11-q13 duplications in psychotic illness. METHOD: The authors scanned 7,582 patients with schizophrenia or schizoaffective disorder and 41,370 comparison subjects without known psychiatric illness for copy number variants at 15q11-q13 and determined the parental origin of duplications using methylation-sensitive Southern hybridization analysis. RESULTS: Duplications were found in four case patients and five comparison subjects. All four case patients had maternally derived duplications (0.05%), while only three of the five comparison duplications were maternally derived (0.007%), resulting in a significant excess of maternally derived duplications in case patients (odds ratio=7.3). This excess is compatible with earlier observations that risk for psychosis in people with Prader-Willi syndrome caused by maternal uniparental disomy is much higher than in those caused by deletion of the paternal chromosome. CONCLUSIONS: These findings suggest that the presence of two maternal copies of a fragment of chromosome 15q11.2-q13.1 that overlaps with the Prader-Willi/Angelman syndrome critical region may be a rare risk factor for schizophrenia and other psychoses. Given that maternal duplications of this region are among the most consistent cytogenetic observations in autism, the findings provide further support for a shared genetic etiology between autism and psychosis. Lundbeck Foundation R34-A3243 Danish National Advanced Technology Foundation 001-2009-2 Danish Council for Independent Research in Medical Sciences Danish Psychiatric Research Foundation European Union (EU) LSHM-CT-2006-037761 HEALTH-2007-2.2.1-10-223423 IMI-JU-NewMeds PIAP-GA-2008-218251 National Institutes of Health MH071425 National Genomic Network (NGFNplus) of the German Federal Ministry of Education and Research (BMBF Wellcome Trust, London Medical Research Council, London info:eu-repo/grantAgreement/EC/FP7/218251
- Published
- 2011
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