Article: Common variants conferring risk of schizophrenia

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TitleCommon variants conferring risk of schizophrenia
AuthorsStefansson, H
Ophoff, RA15 38
Steinberg, S
Andreassen, OA30
Cichon, S3
Rujescu, D
Werge, T4
Pietiläinen, OPH18 29
Mors, O33
Mortensen, PB10
Sigurdsson, E9 22
Gustafsson, O
Nyegaard, M10
TuulioHenriksson, A17
Ingason, A
Hansen, T4
Suvisaari, J17
Lonnqvist, J17
Paunio, T17
Børglum, AD10 33
Hartmann, A
FinkJensen, A28
Nordentoft, M23
Hougaard, D16
NorgaardPedersen, B16
Böttcher, Y
Olesen, J20
Breuer, R21
Möller, HJ1
Giegling, I
Rasmussen, HB4
Timm, S4
Mattheisen, M3
Bitter, I39
Réthelyi, JM39
Magnusdottir, BB9 22
Sigmundsson, T9 22
Olason, P
Masson, G
Gulcher, JR
Haraldsson, M9 22
Fossdal, R
Thorgeirsson, TE
Thorsteinsdottir, U22
Ruggeri, M36
Tosato, S36
Franke, B31
Strengman, E38
Kiemeney, LA31
Melle, I30
Djurovic, S30
Abramova, L19
Kaleda, V19
Sanjuan, J14
De Frutos, R25
Bramon, E2
Vassos, E2
Fraser, G6
Ettinger, U2
Picchioni, M2
Walker, N24
Toulopoulou, T2
Need, AC35
Ge, D35
Lim Yoon, J34
Shianna, KV35
Freimer, NB15
Cantor, RM15 34
Murray, R2
Kong, A
Golimbet, V19
Carracedo, A11
Arango, C5
Costas, J32
Jönsson, EG27
Terenius, L27
Agartz, I27
Petursson, H9 22
Nöthen, MM3
Rietschel, M21
Matthews, PM7
Muglia, P12
Peltonen, L18 29
St Clair, D6
Goldstein, DB35
Stefansson, K22
Collier, DA2 37
Kahn, RS38
Linszen, DH8
Van Os, J26
Wiersma, D13
Bruggeman, R13
Cahn, W38
De Haan, L8
Krabbendam, L26
MyinGermeys, I26
KeywordsChemicals And Cas Registry Numbers
Issue Date2009
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature
CitationNature, 2009, v. 460 n. 7256, p. 744-747 [How to Cite?]
DOI: http://dx.doi.org/10.1038/nature08186
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.
ISSN0028-0836
2011 Impact Factor: 36.28
2011 SCImago Journal Rankings: 7.767
DOIhttp://dx.doi.org/10.1038/nature08186
ISI Accession Number IDWOS:000268670300040
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.

PubMed Central IDPMC3077530
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorStefansson, H
dc.contributor.authorOphoff, RA
dc.contributor.authorSteinberg, S
dc.contributor.authorAndreassen, OA
dc.contributor.authorCichon, S
dc.contributor.authorRujescu, D
dc.contributor.authorWerge, T
dc.contributor.authorPietiläinen, OPH
dc.contributor.authorMors, O
dc.contributor.authorMortensen, PB
dc.contributor.authorSigurdsson, E
dc.contributor.authorGustafsson, O
dc.contributor.authorNyegaard, M
dc.contributor.authorTuulioHenriksson, A
dc.contributor.authorIngason, A
dc.contributor.authorHansen, T
dc.contributor.authorSuvisaari, J
dc.contributor.authorLonnqvist, J
dc.contributor.authorPaunio, T
dc.contributor.authorBørglum, AD
dc.contributor.authorHartmann, A
dc.contributor.authorFinkJensen, A
dc.contributor.authorNordentoft, M
dc.contributor.authorHougaard, D
dc.contributor.authorNorgaardPedersen, B
dc.contributor.authorBöttcher, Y
dc.contributor.authorOlesen, J
dc.contributor.authorBreuer, R
dc.contributor.authorMöller, HJ
dc.contributor.authorGiegling, I
dc.contributor.authorRasmussen, HB
dc.contributor.authorTimm, S
dc.contributor.authorMattheisen, M
dc.contributor.authorBitter, I
dc.contributor.authorRéthelyi, JM
dc.contributor.authorMagnusdottir, BB
dc.contributor.authorSigmundsson, T
dc.contributor.authorOlason, P
dc.contributor.authorMasson, G
dc.contributor.authorGulcher, JR
dc.contributor.authorHaraldsson, M
dc.contributor.authorFossdal, R
dc.contributor.authorThorgeirsson, TE
dc.contributor.authorThorsteinsdottir, U
dc.contributor.authorRuggeri, M
dc.contributor.authorTosato, S
dc.contributor.authorFranke, B
dc.contributor.authorStrengman, E
dc.contributor.authorKiemeney, LA
dc.contributor.authorMelle, I
dc.contributor.authorDjurovic, S
dc.contributor.authorAbramova, L
dc.contributor.authorKaleda, V
dc.contributor.authorSanjuan, J
dc.contributor.authorDe Frutos, R
dc.contributor.authorBramon, E
dc.contributor.authorVassos, E
dc.contributor.authorFraser, G
dc.contributor.authorEttinger, U
dc.contributor.authorPicchioni, M
dc.contributor.authorWalker, N
dc.contributor.authorToulopoulou, T
dc.contributor.authorNeed, AC
dc.contributor.authorGe, D
dc.contributor.authorLim Yoon, J
dc.contributor.authorShianna, KV
dc.contributor.authorFreimer, NB
dc.contributor.authorCantor, RM
dc.contributor.authorMurray, R
dc.contributor.authorKong, A
dc.contributor.authorGolimbet, V
dc.contributor.authorCarracedo, A
dc.contributor.authorArango, C
dc.contributor.authorCostas, J
dc.contributor.authorJönsson, EG
dc.contributor.authorTerenius, L
dc.contributor.authorAgartz, I
dc.contributor.authorPetursson, H
dc.contributor.authorNöthen, MM
dc.contributor.authorRietschel, M
dc.contributor.authorMatthews, PM
dc.contributor.authorMuglia, P
dc.contributor.authorPeltonen, L
dc.contributor.authorSt Clair, D
dc.contributor.authorGoldstein, DB
dc.contributor.authorStefansson, K
dc.contributor.authorCollier, DA
dc.contributor.authorKahn, RS
dc.contributor.authorLinszen, DH
dc.contributor.authorVan Os, J
dc.contributor.authorWiersma, D
dc.contributor.authorBruggeman, R
dc.contributor.authorCahn, W
dc.contributor.authorDe Haan, L
dc.contributor.authorKrabbendam, L
dc.contributor.authorMyinGermeys, I
dc.date.accessioned2011-09-27T03:02:57Z
dc.date.available2011-09-27T03:02:57Z
dc.date.issued2009
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.
dc.description.naturelink_to_subscribed_fulltext
dc.identifier.citationNature, 2009, v. 460 n. 7256, p. 744-747 [How to Cite?]
DOI: http://dx.doi.org/10.1038/nature08186
dc.identifier.citeulike5103475
dc.identifier.doihttp://dx.doi.org/10.1038/nature08186
dc.identifier.eissn1476-4687
dc.identifier.epage747
dc.identifier.isiWOS:000268670300040
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.

dc.identifier.issn0028-0836
2011 Impact Factor: 36.28
2011 SCImago Journal Rankings: 7.767
dc.identifier.issue7256
dc.identifier.pmcidPMC3077530
dc.identifier.pmid19571808
dc.identifier.scopuseid_2-s2.0-68449090594
dc.identifier.spage744
dc.identifier.urihttp://hdl.handle.net/10722/141836
dc.identifier.volume460
dc.languageeng
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature
dc.publisher.placeUnited Kingdom
dc.relation.ispartofNature
dc.relation.referencesReferences in Scopus
dc.subjectChemicals And Cas Registry Numbers
dc.titleCommon variants conferring risk of schizophrenia
dc.typeArticle
Author Affiliations
  1. Ludwig-Maximilians-Universität München
  2. King's College London
  3. Universität Bonn
  4. Copenhagen University Hospital
  5. Hospital General Universitario Gregorio Marañon
  6. University of Aberdeen
  7. Hammersmith Hospital
  8. Academic Medical Centre, University of Amsterdam
  9. National University Hospital Reykjavik
  10. Aarhus Universitet
  11. Universidad de Santiago de Compostela
  12. GlaxoSmithKline
  13. Universitair Medisch Centrum Groningen
  14. Universitat de Valencia, Facultad de Medicina y Odontologia
  15. UCLA Medical Center
  16. Statens Serum Institut
  17. Kansanterveyslaitos
  18. Wellcome Trust Sanger Institute
  19. Russian Academy of Medical Sciences
  20. Amtssygehuset i Glostrup
  21. Universität Heidelberg
  22. University of Iceland
  23. Bispebjerg Hospital
  24. Ravenscraig Hospital
  25. Universitat de Valencia
  26. Maastricht University
  27. Karolinska Institutet
  28. Rigshospitalet
  29. Institute for Molecular Medicine
  30. Universitetet i Oslo
  31. Radboud University Nijmegen Medical Centre
  32. Fundacioarolinan Puarolinablica Galega de Medicina Xenoarolinamica
  33. Ârhus Universitetshospital
  34. University of California, Los Angeles
  35. Duke Institute for Genome Sciences & Policy
  36. Università degli Studi di Verona
  37. Sichuan University
  38. University Medical Center Utrecht
  39. Semmelweis Egyetem