Common variants conferring risk of schizophrenia
| Autor: | Stefansson, H., Ophoff, R. A., Steinberg, S., Andreassen, O. A., Chichon, S., Rujescu, D., Werge, T., Pietilainen, O. P., Mors, O., Mortensen, P. B., Sigurdsson, E., Gustafsson, O., Nyegaard, M., Tuulio Henriksson, A., Ingason, A., Hansen, T., Suvisaari, J., Lonnqvist, J., Paunio, T., Borglum, A. D., Hartmann, A., Fink Jensen, A., Nordentoft, M., Hougaard, D., Norgaard Petersen, B., Bottcher, J., Olesen, J., Breuer, R., Moller, H. J., Giegling, I., Rasmussen, H. B., Timm, S., Mattheisen, M., Bitter, I., Rethelyi, J. M., Magnusdottir, B. B., Sigmundsson, T., Olason, P. I., Masson, G., Gulcher, J. R., Haraldsson, M., Fossdal, R., Thorgeirsson, T. E., Thorsteinsdottir, U., Ruggeri, Mirella, Tosato, Sarah, Franke, B., Strengman, E., Kiemeney, L. A., Group, Melle, I., Djurovic, S., Abramova, I., Kaleda, V., Sanjuan, J., de Frutos, R., Bramon, E., Vassos, E., Fraser, G., Ettinger, U., Picchioni, M., Walker, N., Toulopoulou, T., Need, A. C., Ge, D., Lim Yoon, J., Shianna, K. V., Freimer, N. B., Cator, R. M., Murray, R., Kong, A., Golimbet, V., Carracedo, A., Arango, C., Costas, J., Jonsson, E. G., Terenius, L., Agartz, I., Petursson, H., Nothen, M. M., Rietschel, M., Matthews, P. M., Muglia, P., Peltonen, L., St Clair, D., Goldstein, D. B., Collier, D., Genetic, Risk, Outcome in Psychosis, Kahn, R. S., Linszen, D. H., Van Os, J., Wiersma, D., Bruggeman, R., Cahn, H., de Haan, L., Krabbendam, L., Myin Germeys, I. |
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| Přispěvatelé: | ANS - Amsterdam Neuroscience, Adult Psychiatry, deCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland., Clinical Child and Family Studies, LEARN! - Brain, learning and development, Germeys, Inez |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
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 DNA-Binding Proteins/genetics Genetic Markers/genetics Genome-Wide Association Study Humans Polymorphism Genomic disorders and inherited multi-system disorders [IGMD 3] Molecular epidemiology [NCEBP 1] 03 medical and health sciences Translational research [ONCOL 3] medicine SNP Genetic Predisposition to Disease GENOME-WIDE ASSOCIATION education 030304 developmental biology Genetic association 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 MENTAL-RETARDATION SCAN 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Nature, 460(7256), 744-747. Nature Publishing Group Nature; Vol Stefansson, H, Ophoff, R A, Steinberg, S, Andreassen, O A, Rujescu, D, Werge, T, Cichon, S, Pietiläinen, O P H, Mors, O, Mortensen, P B, Sigurdsson, E, Gustafsson, O, Nyegaard, M, Tuulio-Henriksson, A, Ingason, A, Hansen, T, Suvisaari, J, Lonnqvist, J, Paunio, T, Børglum, A, Hartmann, A, Fink-Jensen, A, Nordentoft, M, Hougaard, D, Norgaard-Pedersen, B, Böttcher, Y, Olesen, J, Breuer, R, Möller, H-J, Giegling, I, Rasmussen, H B, Timm, S, Mattheisen, M, Bitter, I, Réthelyi, J M, Sigmundsson, T, Magnusdottir, B B, Olason, P, Masson, G, Gulcher, J R, Haraldsson, M, Fossdal, R, Thorgeirsson, T E, Thorsteinsdottir, U, Ruggeri, M, Tosato, S, Franke, B, Strengman, E, Group, Kiemeney, L A & Genetic Risk and Outcome in Psychosis (GROUP) 2009, ' Common variants conferring risk of schizophrenia ', Nature, vol. 460, no. 7256, pp. 744-747 . https://doi.org/10.1038/nature08186 Stefansson, H & Krabbendam, L 2009, ' Common variants conferring risk of schizophrenia ', Nature, vol. 460, pp. 744-747 . https://doi.org/10.1038/nature08186 Nature, 460, 744-7 Nature, 460, 7256, pp. 744-7 Nature, 460(7256), 744-U99. Nature Publishing Group Nature Nature, 460, 744-747. Nature Publishing Group |
| ISSN: | 0028-0836 |
| DOI: | 10.1038/nature08186 |
| Popis: | 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. link_to_OA_fulltext |
| Databáze: | OpenAIRE |
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