Common variants conferring risk of schizophrenia

6533b7d7fe1ef96bd1267b81

RESEARCH PRODUCT

Common variants conferring risk of schizophrenia

H. Stefansson R. A. Ophoff S. Steinberg O. A. Andreassen S. Chichon D. Rujescu T. Werge O. P. Pietilainen O. Mors P. B. Mortensen E. Sigurdsson O. Gustafsson M. Nyegaard A. Tuulio Henriksson A. Ingason T. Hansen J. Suvisaari J. Lonnqvist T. Paunio A. D. Borglum A. Hartmann A. Fink Jensen M. Nordentoft D. Hougaard B. Norgaard Petersen J. Bottcher J. Olesen R. Breuer H. J. Moller I. Giegling H. B. Rasmussen S. Timm M. Mattheisen I. Bitter J. M. Rethelyi B. B. Magnusdottir T. Sigmundsson P. I. Olason G. Masson J. R. Gulcher M. Haraldsson R. Fossdal T. E. Thorgeirsson U. Thorsteinsdottir Mirella Ruggeri Sarah Tosato B. Franke E. Strengman L. A. Kiemeney Group I. Melle S. Djurovic I. Abramova V. Kaleda J. Sanjuan R. De Frutos E. Bramon E. Vassos G. Fraser U. Ettinger M. Picchioni N. Walker T. Toulopoulou A. C. Need D. Ge J. Lim Yoon K. V. Shianna N. B. Freimer R. M. Cator R. Murray A. Kong V. Golimbet A. Carracedo C. Arango J. Costas E. G. Jonsson L. Terenius I. Agartz H. Petursson M. M. Nothen M. Rietschel P. M. Matthews P. Muglia L. Peltonen D. St Clair D. B. Goldstein H. Stefansson D. Collier Risk Genetic Outcome In Psychosis R. S. Kahn D. H. Linszen J. Van Os D. Wiersma R. Bruggeman H. Cahn L. De Haan L. Krabbendam I. Myin Germeys

subject

Pair 6/genetics Genetics and epigenetic pathways of disease [NCMLS 6]Genome-wide association study Aetiology screening and detection [ONCOL 5]1Q21.1 Major Histocompatibility Complex/genetics Major Histocompatibility Complex Transcription Factor 4 0302 clinical medicine Chemicals And Cas Registry Numbers Perception and Action [DCN 1]Copy-number variation POPULATION Genetics Pair 18/genetics 0303 health sciences education.field_of_study Genome Human/genetics Multidisciplinary Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Schizophrenia/*genetics/immunology Genetic Predisposition to Disease/*genetics 3. Good health DNA-Binding Proteins Neurogranin/genetics DISEASES Chromosomes Human Pair 6 Single Nucleotide/*genetics Functional Neurogenomics [DCN 2]Zinc finger protein 804A Human Genetic Markers Psychosis Genotype Population Transcription Factors/genetics Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Chromosomes Pair 11/genetics Article Chromosomes; Human; Pair 11/genetics; Pair 18/genetics; Pair 6/genetics; DNA-Binding Proteins/genetics; Genetic Markers/genetics; Genetic Predisposition to Disease/*genetics; Genome; Human/genetics; Genome-Wide Association Study; Genotype; Humans; Major Histocompatibility Complex/genetics; Neurogranin/genetics; Polymorphism; Single Nucleotide/*genetics; Schizophrenia/*genetics/immunology; Transcription Factors/genetics Genomic disorders and inherited multi-system disorders [IGMD 3]Molecular epidemiology [NCEBP 1]03 medical and health sciences Translational research [ONCOL 3]medicine Humans SNP Genetic Predisposition to Disease Polymorphism GENOME-WIDE ASSOCIATION education 030304 developmental biology Genetic association Genetic Markers/genetics Hereditary cancer and cancer-related syndromes [ONCOL 1]Genome Human Chromosomes Human Pair 11 MEMORY medicine.disease GENE NEUROGRANIN DELETIONS Schizophrenia biology.protein Neurogranin Chromosomes Human Pair 18 DNA-Binding Proteins/genetics MENTAL-RETARDATION SCAN 030217 neurology & neurosurgery Genome-Wide Association Study Transcription Factors

description

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 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.

year	journal	country	edition	language
2009-08-06

10.1038/nature08186 https://pure.amc.nl/en/publications/common-variants-conferring-risk-of-schizophrenia(5f90209e-c7bd-40bc-8b26-3d8a832db709).html