eRapport

The role of CNVs in the development of severe mental disorders

Prosjekt
Prosjektnummer
2009048
Ansvarlig person
Ole A. Andreassen
Institusjon
Oslo universitetssykehus HF
Prosjektkategori
Postdoktorstipend
Helsekategori
Mental Health
Forskningsaktivitet
2. Aetiology
Rapporter
2013 - sluttrapport
En av de nyeste genetiske varianter som har blitt tilgjengelig for å utforske er kopitall -varianter i genomet (microdeletions og microduplications), hvor DNA- stykker som strekker seg fra 100 kilobaser til flere basepar enten er fjernet fra en DNA-streng (delesjon) eller kopiert (duplikasjon) på en av DNA-trådene. Noen av disse store variasjoner som er forholdsvis sjeldne, har blitt forbundet med vesentlig økt risiko for alvorlige mentale forstyrrelser slik som schizofreni og autisme. Så langt har det ikke vært mulig å vurdere risikoen forbundet med mindre, kanskje mer vanlige CNVer, i størrelsesorden 10-100 kb , hovedsakelig fordi de fleste datasett bruke lavere tetthet mikro arrays ( ofte 300,000-500,000 prober). Hele den norske TOP kohort er genotypet på mikro - array, noe som gir 1,8 markører som kan brukes for CNV deteksjon. Dette ble brukt for å identifisere CNV i materialet, og kombinere det med andre kohorter i meta-analyser. Prosjektets post doktor har vært forfatter på en rekke fagtidsskrift publikasjoner på kopitallsvarianter assosiert med schizofreni og bipolar lidelse, men også oppmerksomhetssvikt og hyperaktivitet (ADHD). Dette har medført ny kunnskap om genetiske årsakene til disse lidelsene. Postdoktorprosjektet ble utført i nært samarbeid med deCODE genetics, og postdoktoren arbeidet i lengre perioder i Reykjavik. Et viktig resultat var oppdagelsen av nye CNV assosiert med schizofreni. Disse CNVer er sjeldne, men for de som har dem vil sjansen for sykdom øke betraktelig. En annen mye omtalt oppdagelse var koblingen mellom CNV og ADHD, som postdoktoren i prosjektet var involvert i - dette viste at det finnes klare genetisk sårbarhet for denne tilstanden. Prosjektets ressurser har også tidvis blitt brukt på vanlige genetiske varianter, og her har prosjektet også bidratt til ny kunnskap om sårbarhet for schizofreni og bipolar lidelse, men også andre nevropsykiatriske lidelser. Prosjektets resultater har blitt publisert i prestisjetunge internasjonale tidsskrift, slik som Nature, Nature Genetics, Lancet, Molecular Psychiatry. Data generert i dette prosjektet inngår nå i større meta-analyser, spesielt gjennom deltakelse i Psychiatric Genomics Consortium ( PGC ) der data fra prosjektet inngår i et stort multinasjonalt meta -analyse av CNV data om både bipolar lidelse og schizofreni. Disse resultatene er nå under bearbeidelse og artikkel vil bli innsendt i løpet av 2014. På det nåværende tidspunkt kan kunnskap om kopitallsvarianter ikke direkte nyttiggjøres i klinisk praksis, da de er sjeldne og ikke mulig å bruke til screening. Men kunnskapen kan brukes til å forstå noe av mekanismene for hvordan sykdom oppstår, og spesielt innen psykiske lidelser. Det viser seg at noen av disse gen-variantene ikke nedarves, men oppstår etter at kjønnscellene dannes, såkalt de Novo mutasjoner. Det betyr at det ikke er foreldre eller dårlig oppvekstforhold som ligger bak sykdomsutvikling, men en uheldig genetisk variant. Det kan være fint for mange pårørende å vite, som kan slite med skyldfølelse og stigma. Det er også flere pågående prosjekter internasjonalt som bruker resultat oppnådd i dette prosjektet som grunnlag for å utvikle nye medikamenter for bedre å behandle lidelsene.
2012
Recent findings have highlighted the role of large and rare copy number variants (CNVs) in severe psychiatric disorders. In this project the object is to identify novel, small CNVs that that will also contribute a risk for severe mental disorders. The effects of CNVs on structural changes in the brain will also be inspected by MRI-imaging.The TOP research cohort at Oslo University Hospital is a unique resource where genetically homogenous psychiatric patients with very thorough genotyping and phenotyping data are available. The current project is based on collaboration with deCODE Genetics, Iceland, and European Research Network. The entire Norwegian TOP cohort is genotyped on the Affymetrix 6.0 micro-array, giving 1.8 million probes that can be used for CNV detection. This should make it possible to reliably predict smaller CNVs than current studies have reported. The datasets that are generated has been used to find significant enrichment of particular CNVs in schizophrenia, bipolar disorder or psychosis patients when compared to control groups. No genome wide-significant associations have yet been discovered in the CNV analysis of the TOP sample, but the genotyped cohort is constantly being expanded with more samples and the more powerful sample-set could still yield novel results. Furthermore we are now participating in the Psychiatric Genome wide association Consortium (PGC) where the TOP samples are included in a large multi-national meta analysis of CNV data on both bipolar disorder and schizophrenia. That consortium (PGC-CNV; http://pgc.unc.edu) aim to publish a paper on novel copy number variants that confer risk of psychiatric disorders. The TOP dataset is currently included in this large multi-national CNV analysis. At present, 12878 calls were used to evaluate the performance of 4 CNV calling algorithms (C-Score, BirdSuite, PennCNV and Ipattern) in individual or merged segmentors and compared for both deletion and duplication cnvscalls. Sensitivity is measured based on the detection rate of Gold Standard calls by AffyCNV callers, while Specificity is measured by validation rate of AffyCNV callers by Gold Standard. The project provided support for Omar Gustafsson and Lavinia Athanasiu. Gustafsson participated in replication study and meta-analysis in European samples that revealed association of the 3p21.1 locus with bipolar disorder. The results were published in Biological Psychiatry 2012. Athanasiu publishing results from translational psychiatry analysis on TCF4 sequence variants and Genome-wide association study results during psychopharmacological treatment. Now her work is focusing on identifying possible CNVs that are associated with metabolic and cardiovascular risk factors during pharmacological therapy. For this purpose, twelve indicators of metabolic side effects (body mass index (BMI), waist circumference, low density lipoprotein cholesterol, high density lipoprotein cholesterol (HDL-C) , total cholesterol (TG), triglycerides, glucose, HDL-C/TC ratio and C-reactive protein as well as cardiovascular risk factors (blood pressure, heart rate) will be analyzed in a naturalistic sample of 594 patients of Norwegian ancestry. We will analyse interactions between CNVs and three categories of psychopharmacological agents based on their reported potential for side effects and defined genome-wide significance based on false discovery rate of 0.1.
2011
Recent findings have highlighted the role of large and rare copy number variants (CNVs) in severe psychiatric disorders. In this project the object is to identify novel, small CNVs that that will also contribute a risk for severe mental disorders. The effects of CNVs on structural changes in the brain will also be inspected by MRI-imaging.The TOP research cohort at Oslo University Hospital is a unique resource where genetically homogenous psychiatric patients with very thorough genotyping and phenotyping data are available. The current project is based on collaboration with deCODE Genetics, Iceland, and European Research Network. One of the most recent genetic variants that have become available to explore are microdeletions and microduplications; copy number variants (CNV) in the genome where DNA pieces ranging from 100 kilobases to several megabases are either removed from one DNA strand (deletion) or duplicated on one of the DNA strands. Some of these large variations that are relatively rare have been associated with significantly increased risk of severe mental disorders such as schizophrenia and autism. So far it has not been possible to evaluate the risk associated with smaller, perhaps more common CNVs, in the range of 10-100 kb, mainly because most datasets use lower density micro-arrays (frequently 300,000-500,000 probes). The entire Norwegian TOP cohort is genotyped on the Affymetrix 6.0 micro-array, giving 1.8 million probes that can be used for CNV detection. This should make it possible to reliably predict smaller CNVs than current studies have reported. The datasets that will be generated will be used to find significant enrichment of particular CNVs in schizophrenia, bipolar disorder or psychosis patients when compared to control groups. Furthermore the effect of both CNVs and SNPs on structural brain variants obtained via automated analysis of magnetic resonance imaging (MRI) will be inspected using quantitative trait locus (QTL) statistical model. Collaboration with European research groups focusing on psychiatric disorder and structural MRI-imaging has been established previously in the TOP project, and that will be crucial to verify/replicate the outcomes from the coming analysis. Progress so-far: The genotyped TOP data set has been expanded to about 1600 genotyped subjects in 2011, and have been used in several research projects. No genome wide-significant associations have yet been discovered in the CNV analysis of the TOP sample, but the genotyped cohort is constantly being expanded with more samples and the more powerful sample-set could still yield novel results. Furthermore we are now participating in the Psychiatric Genome wide association Consortium (PGC) where the TOP samples are included in a large multi-national meta analysis of CNV data on both bipolar disorder and schizophrenia. That consortium published in 2011 novel genome wide SNP associations for schizophrenia and aim to publish a paper in 2012 on novel copy number variants that confer risk of psychiatric disorders. The TOP dataset is currently included in this large multi-national CNV analysis. The post doc funded by the project, Omar Gustafsson, was a contributing author for twelve peer reviewed journal publications in 2011. These articles involve research in schizophrenia, bipolar disorder and obesity and Parkinson's disease. Currently there is ongoing work on an article on recurring CNVs that are under negative selection, which is being submitted in beginning of 2012.
2010
Recent findings have highlighted the role of large and rare copy number variants (CNVs) in severe psychiatric disorders. In this project we aim to find novel CNVs that are smaller and more common that will also contribute a risk for severe mental disorders. The effect of CNVs on changes in the brain will also be inspected by MRI-imaging.The TOP research cohort at Oslo University Hospital is a unique resource where genetically homogenous psychiatric patients with very thorough genotyping and phenotyping data are available. One of the most recent genetic variants that have become available to explore are microdeletions and microduplications; copy number variants in the genome where DNA pieces ranging from 100 kilobases to several megabases are either removed from one DNA strand (deletion) or duplicated on one of the DNA strands. Some of these large variations that are relatively rare have been associated with significantly increased risk of severe mental disorders such as schizophrenia and autism. So far it has not been possible to evaluate the risk associated with smaller, perhaps more common CNVs, in the range of 10-100 kb, mainly because most datasets use lower density micro-arrays (frequently 300,000-500,000 probes). The entire Norwegian TOP cohort is genotyped on the Affymetrix 6.0 micro-array, giving 1.8 million probes that can be used for CNV detection. This should make it possible to reliably predict smaller CNVs than current studies have reported. The datasets that will be generated will be used to find significant enrichment of particular CNVs in schizophrenia, bipolar disorder or psychosis patients when compared to control groups. Furthermore the effect of both CNVs and SNPs on structural brain variants obtained via automated analysis of magnetic resonance imaging (MRI) will be inspected using quantitative trail locus (QTL) statistical model. Collaboration with European research groups focusing on psychiatric disorder and structural MRI-imaging has been established previously in the TOP project, and that will be crucial to verify/replicate the outcomes from the coming analysis. Progress so-far: There grant recipient was a contributing author on six peer reviewed journal publications in 2010. These articles involve research in schizophrenia, bipolar disorder and attention deficit and hyperactivity disorder (ADHD). Currently there is ongoing work on an article on recurring CNVs that are under negative selection. The genotyped data set has been expanded from about 900 genotyped subjects to about 1500 genotyped subjects in 2010. The data set that is available for brain MRI analysis is currently being expanded from approximately 500 samples to 1500 samples by collaboration with other Norwegian groups. No genome wide-significant associations have yet been discovered in the CNV analysis of the TOP sample, but the genotyped cohort is constantly being expanded with more samples and the more powerful sample-set could still yield novel results. Furthermore we are now participating in the Psychiatric Genome wide association Consortium (PGC) where the TOP samples are included in a large multi-national meta analysis of CNV data on both bipolar disorder and schizophrenia. This allows us to participate in discoveries of novel rare variants that confer risk of psychiatric disorders. The project is set to end in April 2012.
2009
Recent findings have highlighted the role of large and rare copy number variants (CNVs) in severe psychiatric disorders. In this project we aim to find novel CNVs that are smaller and more common that will also contribute risk for severe mental disorders. The effect of CNVs on brain abnormalities will also be inspected by MRI-imaging.The TOP research cohort at Oslo University Hospital is a unique resource where genetically homogenous psychiatric patients with very thorough genotyping and phenotyping data are available. One of the most recent genetic variants that have become available to explore are microdeletions and microduplications; copy number variants in the genome where DNA pieces ranging from 100 kilobases to several megabases are either removed from one DNA strand (deletion) or duplicated on one of the DNA strands. Some of these large variations that are relatively rare have been associated with significantly increased risk of severe mental disorders such as schizophrenia and autism. So far it has not been possible to evaluate the risk associated with smaller, perhaps more common CNVs, in the range of 10-100 kb, mainly because most datasets use lower density micro-arrays (frequently 300,000-500,000 probes). The entire Norwegian TOP cohort is genotyped on the Affymetrix 6.0 micro-array, giving 1.8 million probes that can be used for CNV detection. This should make it possible to reliably predict smaller CNVs than current studies have reported. The datasets that will be generated will be used to find significant enrichment of particular CNVs in schizophrenia, bipolar or psychosis patients when compared to control groups. Furthermore the effect of both CNVs and SNPs on structural brain variants obtained via automated analysis of magnetic resonance imaging (MRI) will be inspected using quantitative trail locus (QTL) statistical model. Studies on fMRI are also planned. Collaboration with European research groups focusing on psychiatric disorder and MRI-imaging has been established previously in the TOP project, and that will be crucial to verify/replicate the outcomes from the coming analysis. Progress so-far: Omar Gustafsson PhD started as a post doc on the project in April 2009, and he is currently working as a guest researcher at DeCODE Genetics, Iceland, where he received training in molecular genetic methods. He has already during his post doc period co-authored 3 articles that have been accepted for publication and will be on PubMed in the coming weeks/months. These articles involve research in the genetic etiology of severe mental disorders, including schizophrenia and addiction. Furthermore, work on a CNV article is in commencing soon. The first genome wide analyses have been performed in the TOP datasets, but these analyses are still too preliminary to provide conclusions. However, the genotyped cohort is currently being extended and the more powerful sample-set will be re-analyzed once the data is available, in spring 2010. Furthermore a protocol has been set up to do a candidate gene approach where known genes that are associated with psychiatric disorders can be tested for association with MRI changes in the brain. The post doc spent one week at the University of San Diego in May 2009 to familiarize himself with the automated analysis of brain MRI data.
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Candidate gene analysis of the human natural killer-1 carbohydrate pathway and perineuronal nets in schizophrenia: B3GAT2 is associated with disease risk and cortical surface area.

Biol Psychiatry 2011 Jan;69(1):90-6. Epub 2010 okt 15

PMID: 20950796

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, PubMed.ItemsChoiceType2[], Nöthen Markus M, Gurling Hugh, O'Donovan Michael C, Owen Michael J, Sigurdsson Engilbert, Petursson Hannes, Stefansson Hreinn, Rujescu Dan, Stefansson Kari, Werge Thomas

Maternally derived microduplications at 15q11-q13: implication of imprinted genes in psychotic illness.

Am J Psychiatry 2011 Apr;168(4):408-17. Epub 2011 feb 15

PMID: 21324950

PubMed.ItemsChoiceType2[], PubMed.ItemsChoiceType2[]

A two-stage meta-analysis identifies several new loci for Parkinson's disease.

PLoS Genet 2011 Jun;7(6):e1002142. Epub 2011 jun 30

PMID: 21738488

Hansen Thomas, Ingason Andrés, Djurovic Srdjan, Melle Ingrid, Fenger Mogens, Gustafsson Omar, Jakobsen Klaus D, Rasmussen Henrik B, Tosato Sarah, Rietschel Marcella, Frank Josef, Owen Mike, Bonetto Chiara, Suvisaari Jaana, Thygesen Johan Hilge, Pétursson Hannes, Lönnqvist Jouko, Sigurdsson Engilbert, Giegling Ina, Craddock Nick, O'Donovan Michael C, Ruggeri Mirella, Cichon Sven, Ophoff Roel A, Pietiläinen Olli, Peltonen Leena, Nöthen Markus M, Rujescu Dan, St Clair David, Collier David A, Andreassen Ole A, Werge Thomas

At-risk variant in TCF7L2 for type II diabetes increases risk of schizophrenia.

Biol Psychiatry 2011 Jul;70(1):59-63. Epub 2011 mar 16

PMID: 21414605

Rietschel M, Mattheisen M, Degenhardt F, eUtils.ItemsChoiceType2[], Mühleisen T W, Kirsch P, Esslinger C, Herms S, Demontis D, Steffens M, Strohmaier J, Haenisch B, Breuer R, Czerski P M, Giegling I, Strengman E, Schmael C, Mors O, Mortensen P B, Hougaard D M, Ørntoft T, Kapelski P, Priebe L, Basmanav F F, Forstner A J, Hoffman P, Meier S, Nikitopoulos J, Moebus S, Alexander M, Mössner R, Wichmann H -E, Schreiber S, Rivandeneira F, Hofman A, Uitterlinden A G, Wienker T F, Schumacher J, Hauser J, Maier W, Cantor R M, Erk S, Schulze T G, eUtils.ItemsChoiceType2[], Craddock N, Owen M J, O'Donovan M C, Børglum A D, Rujescu D, Walter H, Meyer-Lindenberg A, Nöthen N M, Ophoff R A, Cichon S

Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe.

Mol Psychiatry 2012 Sep;17(9):906-17. Epub 2011 jul 12

PMID: 21747397

Olsen Line, Hansen Thomas, Djurovic Srdjan, Haastrup Eva, Albrecthsen Anders, Hoeffding Louise K E, Secher Anna, Gustafsson Omar, Jakobsen Klaus D, Nielsen Finn C, Ullum Henrik, Morken Gunnar, Agartz Ingrid, Melle Ingrid, Gether Ulrik, Andreassen Ole A, Werge Thomas

Copy number variations in affective disorders and meta-analysis.

Psychiatr Genet 2011 Dec;21(6):319-22.

PMID: 21451435

Tesli Martin, Koefoed Pernille, Athanasiu Lavinia, Mattingsdal Morten, Gustafsson Omar, Agartz Ingrid, Rimol Lars M, Brown Andrew, Wirgenes Katrine V, Smorr Lisa-Lena, Kähler Anna K, Werge Thomas, Mors Ole, Mellerup Erling, Jönsson Erik G, Melle Ingrid, Morken Gunnar, Djurovic Srdjan, Andreassen Ole A

Association analysis of ANK3 gene variants in nordic bipolar disorder and schizophrenia case-control samples.

Am J Med Genet B Neuropsychiatr Genet 2011 Dec;156B(8):969-74. Epub 2011 okt 3

PMID: 21972176

PubMed.ItemsChoiceType2[], Nalls Michael A, Plagnol Vincent, Hernandez Dena G, Sharma Manu, Sheerin Una-Marie, Saad Mohamad, Simón-Sánchez J, Schulte Claudia, Lesage Suzanne, Sveinbjörnsdóttir Sigurlaug, Stefánsson Kári, Martinez Maria, Hardy John, Heutink Peter, Brice Alexis, Gasser Thomas, Singleton Andrew B, Wood Nicholas W

Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies.

Lancet 2011 Feb;377(9766):641-9. Epub 2011 feb 1

PMID: 21292315

Williams Nigel M, Zaharieva Irina, Martin Andrew, Langley Kate, Mantripragada Kiran, Fossdal Ragnheidur, Stefansson Hreinn, Stefansson Kari, Magnusson Pall, Gudmundsson Olafur O, Gustafsson Omar, Holmans Peter, Owen Michael J, O'Donovan Michael, Thapar Anita

Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis.

Lancet 2010 Oct;376(9750):1401-8. Epub 2010 sep 29

PMID: 20888040

Tesli Martin, Athanasiu Lavinia, Mattingsdal Morten, Kähler Anna K, Gustafsson Omar, Andreassen Bettina K, Werge Thomas, Hansen Thomas, Mors Ole, Mellerup Erling, Koefoed Pernille, Jönsson Erik G, Agartz Ingrid, Melle Ingrid, Morken Gunnar, Djurovic Srdjan, Andreassen Ole A

Association analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample.

Am J Med Genet B Neuropsychiatr Genet 2010 Oct;153B(7):1276-82.

PMID: 20872766

Djurovic Srdjan, Gustafsson Omar, Mattingsdal Morten, Athanasiu Lavinia, Bjella Thomas, Tesli Martin, Agartz Ingrid, Lorentzen Steinar, Melle Ingrid, Morken Gunnar, Andreassen Ole A

A genome-wide association study of bipolar disorder in Norwegian individuals, followed by replication in Icelandic sample.

J Affect Disord 2010 Oct;126(1-2):312-6. Epub 2010 mai 7

PMID: 20451256

Athanasiu Lavinia, Mattingsdal Morten, Kähler Anna K, Brown Andrew, Gustafsson Omar, Agartz Ingrid, Giegling Ina, Muglia Pierandrea, Cichon Sven, Rietschel Marcella, Pietiläinen Olli P H, Peltonen Leena, Bramon Elvira, Collier David, Clair David St, Sigurdsson Engilbert, Petursson Hannes, Rujescu Dan, Melle Ingrid, Steen Vidar M, Djurovic Srdjan, Andreassen Ole A

Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort.

J Psychiatr Res 2010 Sep;44(12):748-53. Epub 2010 feb 24

PMID: 20185149

Ingason A, Rujescu D, Cichon S, Sigurdsson E, Sigmundsson T, Pietiläinen O P H, Buizer-Voskamp J E, Strengman E, Francks C, Muglia P, Gylfason A, Gustafsson O, Olason P I, Steinberg S, Hansen T, Jakobsen K D, Rasmussen H B, Giegling I, Möller H-J, Hartmann A, Crombie C, Fraser G, Walker N, Lonnqvist J, Suvisaari J, Tuulio-Henriksson A, Bramon E, Kiemeney L A, Franke B, Murray R, Vassos E, Toulopoulou T, Mühleisen T W, Tosato S, Ruggeri M, Djurovic S, Andreassen O A, Zhang Z, Werge T, Ophoff R A, GROUP Investigators, Rietschel M, Nöthen M M, Petursson H, Stefansson H, Peltonen L, Collier D, Stefansson K, Clair D M St

Copy number variations of chromosome 16p13.1 region associated with schizophrenia.

Mol Psychiatry 2009 Sep. Epub 2009 sep 29

PMID: 19786961

Stefansson Hreinn, Ophoff Roel A, Steinberg Stacy, Andreassen Ole A, Cichon Sven, Rujescu Dan, Werge Thomas, Pietiläinen Olli P H, Mors Ole, Mortensen Preben B, Sigurdsson Engilbert, Gustafsson Omar, Nyegaard Mette, Tuulio-Henriksson Annamari, Ingason Andres, Hansen Thomas, Suvisaari Jaana, Lonnqvist Jouko, Paunio Tiina, Børglum Anders D, Hartmann Annette, Fink-Jensen Anders, Nordentoft Merete, Hougaard David, Norgaard-Pedersen Bent, Böttcher Yvonne, Olesen Jes, Breuer René, Möller Hans-Jürgen, Giegling Ina, Rasmussen Henrik B, Timm Sally, Mattheisen Manuel, Bitter István, Réthelyi János M, Magnusdottir Brynja B, Sigmundsson Thordur, Olason Pall, Masson Gisli, Gulcher Jeffrey R, Haraldsson Magnus, Fossdal Ragnheidur, Thorgeirsson Thorgeir E, Thorsteinsdottir Unnur, Ruggeri Mirella, Tosato Sarah, Franke Barbara, Strengman Eric, Kiemeney Lambertus A, Genetic Risk and Outcome in Psychosis (GROUP), Melle Ingrid, Djurovic Srdjan, Abramova Lilia, Kaleda Vasily, Sanjuan Julio, de Frutos Rosa, Bramon Elvira, Vassos Evangelos, Fraser Gillian, Ettinger Ulrich, Picchioni Marco, Walker Nicholas, Toulopoulou Timi, Need Anna C, Ge Dongliang, Yoon Joeng Lim, Shianna Kevin V, Freimer Nelson B, Cantor Rita M, Murray Robin, Kong Augustine, Golimbet Vera, Carracedo Angel, Arango Celso, Costas Javier, Jönsson Erik G, Terenius Lars, Agartz Ingrid, Petursson Hannes, Nöthen Markus M, Rietschel Marcella, Matthews Paul M, Muglia Pierandrea, Peltonen Leena, St Clair David, Goldstein David B, Stefansson Kari, Collier David A

Common variants conferring risk of schizophrenia.

Nature 2009 Aug;460(7256):744-7. Epub 2009 jul 1

PMID: 19571808

Rujescu Dan, Ingason Andres, Cichon Sven, Pietiläinen Olli P H, Barnes Michael R, Toulopoulou Timothea, Picchioni Marco, Vassos Evangelos, Ettinger Ulrich, Bramon Elvira, Murray Robin, Ruggeri Mirella, Tosato Sarah, Bonetto Chiara, Steinberg Stacy, Sigurdsson Engilbert, Sigmundsson Thordur, Petursson Hannes, Gylfason Arnaldur, Olason Pall I, Hardarsson Gudmundur, Jonsdottir Gudrun A, Gustafsson Omar, Fossdal Ragnheidur, Giegling Ina, Möller Hans-Jürgen, Hartmann Annette M, Hoffmann Per, Crombie Caroline, Fraser Gillian, Walker Nicholas, Lonnqvist Jouko, Suvisaari Jaana, Tuulio-Henriksson Annamari, Djurovic Srdjan, Melle Ingrid, Andreassen Ole A, Hansen Thomas, Werge Thomas, Kiemeney Lambertus A, Franke Barbara, Veltman Joris, Buizer-Voskamp Jacobine E, GROUP Investigators, Sabatti Chiara, Ophoff Roel A, Rietschel Marcella, Nöthen Markus M, Stefansson Kari, Peltonen Leena, St Clair David, Stefansson Hreinn, Collier David A

Disruption of the neurexin 1 gene is associated with schizophrenia.

Hum Mol Genet 2009 Mar;18(5):988-96. Epub 2008 okt 22

PMID: 18945720

Deltagere
  • Ole Andreas Andreassen Prosjektleder
  • Srdjan Djurovic Forskningsgruppeleder
  • Lavinia Athanasiu Postdoktorstipendiat

eRapport er utarbeidet av Sølvi Lerfald og Reidar Thorstensen, Regionalt kompetansesenter for klinisk forskning, Helse Vest RHF, og videreutvikles av de fire RHF-ene i fellesskap, med støtte fra Helse Vest IKT

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