1. Common variants conferring risk of schizophrenia
- Author
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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., ANS - Amsterdam Neuroscience, Adult Psychiatry, deCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland., Clinical Child and Family Studies, LEARN! - Brain, learning and development, and Germeys, Inez
- Subjects
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 - Abstract
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
- Published
- 2009
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