File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Common variants conferring risk of schizophrenia

TitleCommon variants conferring risk of schizophrenia
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2009
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature
Citation
Nature, 2009, v. 460 n. 7256, p. 744-747 How to Cite?
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 ĝ€ genomic disordersĝ€™, 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. © 2009 Macmillan Publishers Limited.
Persistent Identifierhttp://hdl.handle.net/10722/141836
ISSN
2023 Impact Factor: 50.5
2023 SCImago Journal Rankings: 18.509
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
EULSHM-CT-2006-037761
PIAP-GA-2008-218251
HEALTH-F2-2009-223423
NIMHR01 MH078075
German Federal Ministry of Education and ResearchNGFN-2
Marie CuriePIAP-GA-2008-218251
GlaxoSmithKline
National Institutes of Health1R01HL087679-01
STAMPEED
Funding Information:

We thank the subjects and their relatives and staff at the recruitment centres. This work was sponsored by EU grants LSHM-CT-2006-037761 (Project SGENE), PIAP-GA-2008-218251 (Project PsychGene) and HEALTH-F2-2009-223423 (Project PsychCNVs). Genotyping of the Dutch samples was sponsored by NIMH funding, R01 MH078075. This work was also supported by the National Genomic Network (NGFN-2) of the German Federal Ministry of Education and Research (BMBF) and Marie Curie grant PIAP-GA-2008-218251 (PsychGene). M. M. N. received support from the Alfried Krupp von Bohlen und Halbach-Stiftung. We are grateful to S. Schreiber and M. Krawczak for providing genotype data for PopGen controls, and to K.-H. Jockel and R. Erbel for providing control individuals from the Heinz Nixdorf Recall Study. Recruitment of the patients from Munich was partially supported by GlaxoSmithKline. We are grateful to the Genetics Research Centre GmbH, an initiative by GlaxoSmithKline and LMU. The Northern Finland Birth Cohort 1966 (NFBC66) is thanked for providing population controls for the study. The genotyping of NFBC66 was financially supported by National Institutes of Health grant 1R01HL087679-01, STAMPEED.

References

 

DC FieldValueLanguage
dc.contributor.authorStefansson, Hen_HK
dc.contributor.authorOphoff, RAen_HK
dc.contributor.authorSteinberg, Sen_HK
dc.contributor.authorAndreassen, OAen_HK
dc.contributor.authorCichon, Sen_HK
dc.contributor.authorRujescu, Den_HK
dc.contributor.authorWerge, Ten_HK
dc.contributor.authorPietiläinen, OPHen_HK
dc.contributor.authorMors, Oen_HK
dc.contributor.authorMortensen, PBen_HK
dc.contributor.authorSigurdsson, Een_HK
dc.contributor.authorGustafsson, Oen_HK
dc.contributor.authorNyegaard, Men_HK
dc.contributor.authorTuulioHenriksson, Aen_HK
dc.contributor.authorIngason, Aen_HK
dc.contributor.authorHansen, Ten_HK
dc.contributor.authorSuvisaari, Jen_HK
dc.contributor.authorLonnqvist, Jen_HK
dc.contributor.authorPaunio, Ten_HK
dc.contributor.authorBørglum, ADen_HK
dc.contributor.authorHartmann, Aen_HK
dc.contributor.authorFinkJensen, Aen_HK
dc.contributor.authorNordentoft, Men_HK
dc.contributor.authorHougaard, Den_HK
dc.contributor.authorNorgaardPedersen, Ben_HK
dc.contributor.authorBöttcher, Yen_HK
dc.contributor.authorOlesen, Jen_HK
dc.contributor.authorBreuer, Ren_HK
dc.contributor.authorMöller, HJen_HK
dc.contributor.authorGiegling, Ien_HK
dc.contributor.authorRasmussen, HBen_HK
dc.contributor.authorTimm, Sen_HK
dc.contributor.authorMattheisen, Men_HK
dc.contributor.authorBitter, Ien_HK
dc.contributor.authorRéthelyi, JMen_HK
dc.contributor.authorMagnusdottir, BBen_HK
dc.contributor.authorSigmundsson, Ten_HK
dc.contributor.authorOlason, Pen_HK
dc.contributor.authorMasson, Gen_HK
dc.contributor.authorGulcher, JRen_HK
dc.contributor.authorHaraldsson, Men_HK
dc.contributor.authorFossdal, Ren_HK
dc.contributor.authorThorgeirsson, TEen_HK
dc.contributor.authorThorsteinsdottir, Uen_HK
dc.contributor.authorRuggeri, Men_HK
dc.contributor.authorTosato, Sen_HK
dc.contributor.authorFranke, Ben_HK
dc.contributor.authorStrengman, Een_HK
dc.contributor.authorKiemeney, LAen_HK
dc.contributor.authorMelle, Ien_HK
dc.contributor.authorDjurovic, Sen_HK
dc.contributor.authorAbramova, Len_HK
dc.contributor.authorKaleda, Ven_HK
dc.contributor.authorSanjuan, Jen_HK
dc.contributor.authorDe Frutos, Ren_HK
dc.contributor.authorBramon, Een_HK
dc.contributor.authorVassos, Een_HK
dc.contributor.authorFraser, Gen_HK
dc.contributor.authorEttinger, Uen_HK
dc.contributor.authorPicchioni, Men_HK
dc.contributor.authorWalker, Nen_HK
dc.contributor.authorToulopoulou, Ten_HK
dc.contributor.authorNeed, ACen_HK
dc.contributor.authorGe, Den_HK
dc.contributor.authorLim Yoon, Jen_HK
dc.contributor.authorShianna, KVen_HK
dc.contributor.authorFreimer, NBen_HK
dc.contributor.authorCantor, RMen_HK
dc.contributor.authorMurray, Ren_HK
dc.contributor.authorKong, Aen_HK
dc.contributor.authorGolimbet, Ven_HK
dc.contributor.authorCarracedo, Aen_HK
dc.contributor.authorArango, Cen_HK
dc.contributor.authorCostas, Jen_HK
dc.contributor.authorJönsson, EGen_HK
dc.contributor.authorTerenius, Len_HK
dc.contributor.authorAgartz, Ien_HK
dc.contributor.authorPetursson, Hen_HK
dc.contributor.authorNöthen, MMen_HK
dc.contributor.authorRietschel, Men_HK
dc.contributor.authorMatthews, PMen_HK
dc.contributor.authorMuglia, Pen_HK
dc.contributor.authorPeltonen, Len_HK
dc.contributor.authorSt Clair, Den_HK
dc.contributor.authorGoldstein, DBen_HK
dc.contributor.authorStefansson, Ken_HK
dc.contributor.authorCollier, DAen_HK
dc.contributor.authorKahn, RSen_HK
dc.contributor.authorLinszen, DHen_HK
dc.contributor.authorVan Os, Jen_HK
dc.contributor.authorWiersma, Den_HK
dc.contributor.authorBruggeman, Ren_HK
dc.contributor.authorCahn, Wen_HK
dc.contributor.authorDe Haan, Len_HK
dc.contributor.authorKrabbendam, Len_HK
dc.contributor.authorMyinGermeys, Ien_HK
dc.date.accessioned2011-09-27T03:02:57Z-
dc.date.available2011-09-27T03:02:57Z-
dc.date.issued2009en_HK
dc.identifier.citationNature, 2009, v. 460 n. 7256, p. 744-747en_HK
dc.identifier.issn0028-0836en_HK
dc.identifier.urihttp://hdl.handle.net/10722/141836-
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 ĝ€ genomic disordersĝ€™, 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. © 2009 Macmillan Publishers Limited.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/natureen_HK
dc.relation.ispartofNatureen_HK
dc.subjectChemicals And Cas Registry Numbersen_US
dc.titleCommon variants conferring risk of schizophreniaen_HK
dc.typeArticleen_HK
dc.identifier.emailToulopoulou, T:timothea@hku.hken_HK
dc.identifier.authorityToulopoulou, T=rp01542en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1038/nature08186en_HK
dc.identifier.pmid19571808-
dc.identifier.pmcidPMC3077530-
dc.identifier.scopuseid_2-s2.0-68449090594en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-68449090594&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume460en_HK
dc.identifier.issue7256en_HK
dc.identifier.spage744en_HK
dc.identifier.epage747en_HK
dc.identifier.eissn1476-4687-
dc.identifier.isiWOS:000268670300040-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.f10002136989-
dc.identifier.scopusauthoridStefansson, H=6604083232en_HK
dc.identifier.scopusauthoridOphoff, RA=7004321340en_HK
dc.identifier.scopusauthoridSteinberg, S=22735361200en_HK
dc.identifier.scopusauthoridAndreassen, OA=7005761947en_HK
dc.identifier.scopusauthoridCichon, S=7005957855en_HK
dc.identifier.scopusauthoridRujescu, D=6701768114en_HK
dc.identifier.scopusauthoridWerge, T=6701738296en_HK
dc.identifier.scopusauthoridPietiläinen, OPH=35262502200en_HK
dc.identifier.scopusauthoridMors, O=7004006411en_HK
dc.identifier.scopusauthoridMortensen, PB=7102903327en_HK
dc.identifier.scopusauthoridSigurdsson, E=7004378235en_HK
dc.identifier.scopusauthoridGustafsson, O=26023239200en_HK
dc.identifier.scopusauthoridNyegaard, M=6507330413en_HK
dc.identifier.scopusauthoridTuulioHenriksson, A=35235635600en_HK
dc.identifier.scopusauthoridIngason, A=22734427200en_HK
dc.identifier.scopusauthoridHansen, T=7401667958en_HK
dc.identifier.scopusauthoridSuvisaari, J=35238930800en_HK
dc.identifier.scopusauthoridLonnqvist, J=35234007300en_HK
dc.identifier.scopusauthoridPaunio, T=7003887598en_HK
dc.identifier.scopusauthoridBørglum, AD=7004609664en_HK
dc.identifier.scopusauthoridHartmann, A=7402943568en_HK
dc.identifier.scopusauthoridFinkJensen, A=7004063091en_HK
dc.identifier.scopusauthoridNordentoft, M=7006191523en_HK
dc.identifier.scopusauthoridHougaard, D=7003632207en_HK
dc.identifier.scopusauthoridNorgaardPedersen, B=7005009235en_HK
dc.identifier.scopusauthoridBöttcher, Y=15519086800en_HK
dc.identifier.scopusauthoridOlesen, J=7202911666en_HK
dc.identifier.scopusauthoridBreuer, R=25923810900en_HK
dc.identifier.scopusauthoridMöller, HJ=7401855577en_HK
dc.identifier.scopusauthoridGiegling, I=6602186623en_HK
dc.identifier.scopusauthoridRasmussen, HB=21135869800en_HK
dc.identifier.scopusauthoridTimm, S=12797925400en_HK
dc.identifier.scopusauthoridMattheisen, M=8636730800en_HK
dc.identifier.scopusauthoridBitter, I=26657913300en_HK
dc.identifier.scopusauthoridRéthelyi, JM=6602415594en_HK
dc.identifier.scopusauthoridMagnusdottir, BB=22734737700en_HK
dc.identifier.scopusauthoridSigmundsson, T=6602171613en_HK
dc.identifier.scopusauthoridOlason, P=8547202600en_HK
dc.identifier.scopusauthoridMasson, G=8121805400en_HK
dc.identifier.scopusauthoridGulcher, JR=7006128347en_HK
dc.identifier.scopusauthoridHaraldsson, M=23501321700en_HK
dc.identifier.scopusauthoridFossdal, R=35326461300en_HK
dc.identifier.scopusauthoridThorgeirsson, TE=6701732081en_HK
dc.identifier.scopusauthoridThorsteinsdottir, U=6602988969en_HK
dc.identifier.scopusauthoridRuggeri, M=7005660435en_HK
dc.identifier.scopusauthoridTosato, S=8672074400en_HK
dc.identifier.scopusauthoridFranke, B=7005326255en_HK
dc.identifier.scopusauthoridStrengman, E=6506197520en_HK
dc.identifier.scopusauthoridKiemeney, LA=7005158534en_HK
dc.identifier.scopusauthoridMelle, I=6603091220en_HK
dc.identifier.scopusauthoridDjurovic, S=7003849042en_HK
dc.identifier.scopusauthoridAbramova, L=7006286572en_HK
dc.identifier.scopusauthoridKaleda, V=8906286900en_HK
dc.identifier.scopusauthoridSanjuan, J=7005631069en_HK
dc.identifier.scopusauthoridDe Frutos, R=7003409879en_HK
dc.identifier.scopusauthoridBramon, E=8089378900en_HK
dc.identifier.scopusauthoridVassos, E=35369293900en_HK
dc.identifier.scopusauthoridFraser, G=34770971900en_HK
dc.identifier.scopusauthoridEttinger, U=6602766172en_HK
dc.identifier.scopusauthoridPicchioni, M=6507443795en_HK
dc.identifier.scopusauthoridWalker, N=7201514664en_HK
dc.identifier.scopusauthoridToulopoulou, T=8855468700en_HK
dc.identifier.scopusauthoridNeed, AC=9746096700en_HK
dc.identifier.scopusauthoridGe, D=8963757100en_HK
dc.identifier.scopusauthoridLim Yoon, J=26658636300en_HK
dc.identifier.scopusauthoridShianna, KV=6508389190en_HK
dc.identifier.scopusauthoridFreimer, NB=7006012650en_HK
dc.identifier.scopusauthoridCantor, RM=35375307600en_HK
dc.identifier.scopusauthoridMurray, R=35406239400en_HK
dc.identifier.scopusauthoridKong, A=34667880600en_HK
dc.identifier.scopusauthoridGolimbet, V=7004106288en_HK
dc.identifier.scopusauthoridCarracedo, A=7006062179en_HK
dc.identifier.scopusauthoridArango, C=7004644073en_HK
dc.identifier.scopusauthoridCostas, J=7003291456en_HK
dc.identifier.scopusauthoridJönsson, EG=35393905700en_HK
dc.identifier.scopusauthoridTerenius, L=7102775573en_HK
dc.identifier.scopusauthoridAgartz, I=6701604751en_HK
dc.identifier.scopusauthoridPetursson, H=7003947853en_HK
dc.identifier.scopusauthoridNöthen, MM=35355123900en_HK
dc.identifier.scopusauthoridRietschel, M=7006620620en_HK
dc.identifier.scopusauthoridMatthews, PM=7202324607en_HK
dc.identifier.scopusauthoridMuglia, P=6602544336en_HK
dc.identifier.scopusauthoridPeltonen, L=36051313500en_HK
dc.identifier.scopusauthoridSt Clair, D=35354078200en_HK
dc.identifier.scopusauthoridGoldstein, DB=7402147672en_HK
dc.identifier.scopusauthoridStefansson, K=7005997553en_HK
dc.identifier.scopusauthoridCollier, DA=26642980600en_HK
dc.identifier.scopusauthoridKahn, RS=34770062700en_HK
dc.identifier.scopusauthoridLinszen, DH=7007173948en_HK
dc.identifier.scopusauthoridVan Os, J=7102358027en_HK
dc.identifier.scopusauthoridWiersma, D=7101791155en_HK
dc.identifier.scopusauthoridBruggeman, R=22933600300en_HK
dc.identifier.scopusauthoridCahn, W=6603045753en_HK
dc.identifier.scopusauthoridDe Haan, L=7005592387en_HK
dc.identifier.scopusauthoridKrabbendam, L=6604013856en_HK
dc.identifier.scopusauthoridMyinGermeys, I=6603917483en_HK
dc.identifier.citeulike5103475-
dc.identifier.issnl0028-0836-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats