Journal
AMERICAN JOURNAL OF PSYCHIATRY
Volume 168, Issue 4, Pages 408-417Publisher
AMER PSYCHIATRIC PUBLISHING, INC
DOI: 10.1176/appi.ajp.2010.09111660
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Funding
- 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
- Medical Research Council [G0801418B, G1000708, G0701007] Funding Source: researchfish
- MRC [G0701007, G1000708] Funding Source: UKRI
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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.
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