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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
2014 Impact Factor: 41.456
2014 SCImago Journal Rankings: 17.313
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
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dc.contributor.authorThorsteinsdottir, Uen_HK
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dc.contributor.authorTosato, Sen_HK
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dc.contributor.authorStrengman, Een_HK
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dc.contributor.authorLinszen, DHen_HK
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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
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dc.identifier.scopusauthoridMyinGermeys, I=6603917483en_HK
dc.identifier.citeulike5103475-

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