Maternally Derived Microduplications at 15q11-q13: Implication of Imprinted Genes in Psychotic Illness
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Maternally Derived Microduplications at 15q11-q13: Implication of Imprinted Genes in Psychotic Illness. / 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; GROUP Investigators.
In: American Journal of Psychiatry, Vol. 168, No. 4, 01.04.2011, p. 408-417.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Maternally Derived Microduplications at 15q11-q13: Implication of Imprinted Genes in Psychotic Illness
AU - Ingason, Andrés
AU - Kirov, George
AU - Giegling, Ina
AU - Hansen, Thomas
AU - Isles, Anthony R
AU - Jakobsen, Klaus D
AU - Kristinsson, Kari T
AU - le Roux, Louise
AU - Gustafsson, Omar
AU - Craddock, Nick
AU - Möller, Hans-Jürgen
AU - McQuillin, Andrew
AU - Muglia, Pierandrea
AU - Cichon, Sven
AU - Rietschel, Marcella
AU - Ophoff, Roel A
AU - Djurovic, Srdjan
AU - Andreassen, Ole A
AU - Pietiläinen, Olli P H
AU - Peltonen, Leena
AU - Dempster, Emma
AU - Collier, David A
AU - St Clair, David
AU - Rasmussen, Henrik B
AU - Glenthøj, Birte Y
AU - Kiemeney, Lambertus A
AU - Franke, Barbara
AU - Tosato, Sarah
AU - Bonetto, Chiara
AU - Saemundsen, Evald
AU - Hreidarsson, Stefán J
AU - Nöthen, Markus M
AU - Gurling, Hugh
AU - O'Donovan, Michael C
AU - Owen, Michael J
AU - Sigurdsson, Engilbert
AU - Petursson, Hannes
AU - Stefansson, Hreinn
AU - Rujescu, Dan
AU - Stefansson, Kari
AU - Werge, Thomas
AU - GROUP Investigators
PY - 2011/4/1
Y1 - 2011/4/1
N2 - 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.
AB - 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.
U2 - 10.1176/appi.ajp.2010.09111660
DO - 10.1176/appi.ajp.2010.09111660
M3 - Journal article
C2 - 21324950
VL - 168
SP - 408
EP - 417
JO - The American Journal of Psychiatry
JF - The American Journal of Psychiatry
SN - 0002-953X
IS - 4
ER -
ID: 34046124