2.50
Hdl Handle:
http://hdl.handle.net/2336/86997
Title:
Common variants conferring risk of schizophrenia.
Authors:
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; 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
Citation:
Nature 2009, 460(7256):744-7
Issue Date:
6-Aug-2009
Abstract:
Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1038/nature08186; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077530/
Rights:
openAccess

Full metadata record

DC FieldValue Language
dc.contributor.authorStefansson, Hreinnen
dc.contributor.authorOphoff, Roel Aen
dc.contributor.authorSteinberg, Stacyen
dc.contributor.authorAndreassen, Ole Aen
dc.contributor.authorCichon, Svenen
dc.contributor.authorRujescu, Danen
dc.contributor.authorWerge, Thomasen
dc.contributor.authorPietiläinen, Olli P Hen
dc.contributor.authorMors, Oleen
dc.contributor.authorMortensen, Preben Ben
dc.contributor.authorSigurdsson, Engilberten
dc.contributor.authorGustafsson, Omaren
dc.contributor.authorNyegaard, Metteen
dc.contributor.authorTuulio-Henriksson, Annamarien
dc.contributor.authorIngason, Andresen
dc.contributor.authorHansen, Thomasen
dc.contributor.authorSuvisaari, Jaanaen
dc.contributor.authorLonnqvist, Joukoen
dc.contributor.authorPaunio, Tiinaen
dc.contributor.authorBørglum, Anders Den
dc.contributor.authorHartmann, Annetteen
dc.contributor.authorFink-Jensen, Andersen
dc.contributor.authorNordentoft, Mereteen
dc.contributor.authorHougaard, Daviden
dc.contributor.authorNorgaard-Pedersen, Benten
dc.contributor.authorBöttcher, Yvonneen
dc.contributor.authorOlesen, Jesen
dc.contributor.authorBreuer, Renéen
dc.contributor.authorMöller, Hans-Jürgenen
dc.contributor.authorGiegling, Inaen
dc.contributor.authorRasmussen, Henrik Ben
dc.contributor.authorTimm, Sallyen
dc.contributor.authorMattheisen, Manuelen
dc.contributor.authorBitter, Istvánen
dc.contributor.authorRéthelyi, János Men
dc.contributor.authorMagnusdottir, Brynja Ben
dc.contributor.authorSigmundsson, Thorduren
dc.contributor.authorOlason, Pallen
dc.contributor.authorMasson, Gislien
dc.contributor.authorGulcher, Jeffrey Ren
dc.contributor.authorHaraldsson, Magnusen
dc.contributor.authorFossdal, Ragnheiduren
dc.contributor.authorThorgeirsson, Thorgeir Een
dc.contributor.authorThorsteinsdottir, Unnuren
dc.contributor.authorRuggeri, Mirellaen
dc.contributor.authorTosato, Sarahen
dc.contributor.authorFranke, Barbaraen
dc.contributor.authorStrengman, Ericen
dc.contributor.authorKiemeney, Lambertus Aen
dc.contributor.authorMelle, Ingriden
dc.contributor.authorDjurovic, Srdjanen
dc.contributor.authorAbramova, Liliaen
dc.contributor.authorKaleda, Vasilyen
dc.contributor.authorSanjuan, Julioen
dc.contributor.authorde Frutos, Rosaen
dc.contributor.authorBramon, Elviraen
dc.contributor.authorVassos, Evangelosen
dc.contributor.authorFraser, Gillianen
dc.contributor.authorEttinger, Ulrichen
dc.contributor.authorPicchioni, Marcoen
dc.contributor.authorWalker, Nicholasen
dc.contributor.authorToulopoulou, Timien
dc.contributor.authorNeed, Anna Cen
dc.contributor.authorGe, Dongliangen
dc.contributor.authorYoon, Joeng Limen
dc.contributor.authorShianna, Kevin Ven
dc.contributor.authorFreimer, Nelson Ben
dc.contributor.authorCantor, Rita Men
dc.contributor.authorMurray, Robinen
dc.contributor.authorKong, Augustineen
dc.contributor.authorGolimbet, Veraen
dc.contributor.authorCarracedo, Angelen
dc.contributor.authorArango, Celsoen
dc.contributor.authorCostas, Javieren
dc.contributor.authorJönsson, Erik Gen
dc.contributor.authorTerenius, Larsen
dc.contributor.authorAgartz, Ingriden
dc.contributor.authorPetursson, Hannesen
dc.contributor.authorNöthen, Markus Men
dc.contributor.authorRietschel, Marcellaen
dc.contributor.authorMatthews, Paul Men
dc.contributor.authorMuglia, Pierandreaen
dc.contributor.authorPeltonen, Leenaen
dc.contributor.authorSt Clair, Daviden
dc.contributor.authorGoldstein, David Ben
dc.contributor.authorStefansson, Karien
dc.contributor.authorCollier, David Aen
dc.date.accessioned2009-11-27T11:54:02Zen
dc.date.available2009-11-27T11:54:02Zen
dc.date.issued2009-08-06en
dc.date.submitted2009-11-27en
dc.identifier.citationNature 2009, 460(7256):744-7en
dc.identifier.issn1476-4687en
dc.identifier.pmid19571808en
dc.identifier.doi10.1038/nature08186en
dc.identifier.urihttp://hdl.handle.net/2336/86997en
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractSchizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.en
dc.description.sponsorshipinfo:eu-repo/grantAgreement/EC/FP7/223423 EU LSHM-CT-2006-037761 PIAP-GA-2008-218251 HEALTH-F2-2009-223423 NIMH R01 MH078075 German Federal Ministry of Education and Research NGFN-2 Marie Curie PIAP-GA-2008-218251 GlaxoSmithKline National Institutes of Health 1R01HL087679-01 STAMPEEDen
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/223423en
dc.relation.urlhttp://dx.doi.org/10.1038/nature08186en
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077530/en
dc.rightsopenAccessen
dc.subject.meshChromosomes, Human, Pair 11en
dc.subject.meshChromosomes, Human, Pair 18en
dc.subject.meshChromosomes, Human, Pair 6en
dc.subject.meshDNA-Binding Proteinsen
dc.subject.meshGenetic Markersen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshGenome, Humanen
dc.subject.meshGenome-Wide Association Studyen
dc.subject.meshGenotypeen
dc.subject.meshHumansen
dc.subject.meshMajor Histocompatibility Complexen
dc.subject.meshNeurograninen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshSchizophreniaen
dc.subject.meshTranscription Factorsen
dc.titleCommon variants conferring risk of schizophrenia.en
dc.typeArticleen
dc.contributor.departmentdeCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.en
dc.identifier.journalNatureen

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