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Common variants conferring risk of schizophrenia
Open accessAbstract
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 'genomic disorders', 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.
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“Further, results from SGENE+ 60 implicate NRGN (neurogranin) which may act as a calcium sensor. 61”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [61]
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Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
Inference of Population Structure Using Multilocus Genotype Data
Pritchard, J. K., Stephens, M., & Donnelly, P. (2000) · Genetics · doi:10.1093/genetics/155.2.945 · Cited by 33,871
Statistical Aspects of the Analysis of Data From Retrospective Studies of Disease
(1959) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/22.4.719 · Cited by 14,689
A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566
Statistical Methods for Research Workers
Fisher, R. A. (1945) · American Journal of Clinical Pathology · doi:10.1093/ajcp/15.11.552b · Cited by 10,883
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442
Self-citationCommon polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821
Genomic Control for Association Studies
Devlin, B., & Roeder, K. (1999) · Biometrics · doi:10.1111/j.0006-341x.1999.00997.x · Cited by 3,162
The Wellcome Trust Case Control Consortium, U.K.
Mossman, K. (2008) · Scientific American · doi:10.1038/scientificamerican0108-42a · Cited by 2,714
Large recurrent microdeletions associated with schizophrenia.
GROUP, Stefansson, H., Rujescu, D., Cichon, S., Pietiläinen, O. P. H., Ingason, A., Steinberg, S., Fossdal, R., Sigurdsson, E., Sigmundsson, T., et al. (2008) · Nature · doi:10.1038/nature07229 · Cited by 1,745
Self-citationRare chromosomal deletions and duplications increase risk of schizophrenia
The International Schizophrenia Consortium (2008) · Nature · doi:10.1038/nature07239 · Cited by 1,475
Control of Synaptic Strength by Glial TNFα
Beattie, E. C., Stellwagen, D., Morishita, W., Bresnahan, J. C., Ha, B. K., Von Zastrow, M., Beattie, M. S., & Malenka, R. C. (2002) · Science · doi:10.1126/science.1067859 · Cited by 1,344
The International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), Harley, J. B., Alarcón-Riquelme, M. E., Criswell, L. A., Jacob, C. O., Kimberly, R. P., Moser, K. L., Tsao, B. P., Vyse, T. J., & Langefeld, C. D. (2008) · Nature Genetics · doi:10.1038/ng.81 · Cited by 1,309
Common variants on chromosome 6p22.1 are associated with schizophrenia
Shi, J., Levinson, D. F., Duan, J., Sanders, A. R., Zheng, Y., Pe’er, I., Dudbridge, F., Holmans, P., Whittemore, A. S., Mowry, B. J., et al. (2009) · Nature · doi:10.1038/nature08192 · Cited by 1,154
Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: Schizophrenia
Lewis, C. M., Levinson, D. F., Wise, L. H., DeLisi, L. E., Straub, R. E., Hovatta, I., Williams, N. M., Schwab, S. G., Pulver, A. E., Faraone, S. V., et al. (2003) · The American Journal of Human Genetics · doi:10.1086/376549 · Cited by 1,134
Self-citationRecurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes
Mefford, H. C., Sharp, A. J., Baker, C., Itsara, A., Jiang, Z., Buysse, K., Huang, S., Maloney, V. K., Crolla, J. A., Baralle, D., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0805384 · Cited by 804
van Heel, D. A., Franke, L., Hunt, K. A., Gwilliam, R., Zhernakova, A., Inouye, M., Wapenaar, M. C., Barnardo, M., Bethel, G., Holmes, G. K. T., et al. (2007) · Nature Genetics · doi:10.1038/ng2058 · Cited by 662
Brunetti-Pierri, N., Berg, J. S., Scaglia, F., Belmont, J., Bacino, C. A., Sahoo, T., Lalani, S. R., Graham, B., Lee, B., Shinawi, M., et al. (2008) · Nature Genetics · doi:10.1038/ng.279 · Cited by 625
The gene encoding phosphodiesterase 4D confers risk of ischemic stroke
Grétarsdóttir, S., Þorleifsson, G., Reynisdottir, S. T., Manolescu, A. R., Jonsdottir, S., Jónsdóttir, Þ., Gudmundsdottir, T., Bjarnadottir, S. M., Einarsson, O. B., Gudjonsdottir, H. M., et al. (2003) · Nature Genetics · doi:10.1038/ng1245 · Cited by 560
Self-citationAssociation of Schizophrenia and Autoimmune Diseases: Linkage of Danish National Registers
Eaton, W. W., Byrne, M., Ewald, H., Mors, O., Chen, C.-Y., Agerbo, E., & Mortensen, P. B. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.3.521 · Cited by 527
Self-citationDetection of sharing by descent, long-range phasing and haplotype imputation
Kong, A., Masson, G., Frigge, M. L., Gylfason, A., Zusmanovich, P., Thorleifsson, G., Olason, P. I., Ingason, A., Steinberg, S., Rafnar, T., et al. (2008) · Nature Genetics · doi:10.1038/ng.216 · Cited by 447
Self-citationGene Ontology Analysis of GWA Study Data Sets Provides Insights into the Biology of Bipolar Disorder
Holmans, P., Green, E. K., Pahwa, J. S., Ferreira, M. A. R., Purcell, S. M., Sklar, P., Owen, M. J., O'Donovan, M. C., & Craddock, N. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.05.011 · Cited by 378
Impaired glutathione synthesis in schizophrenia: Convergent genetic and functional evidence
Gysin, R., Kraftsik, R., Sandell, J., Bovet, P., Chappuis, C., Conus, P., Deppen, P., Preisig, M., Ruiz, V., Steullet, P., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706778104 · Cited by 309
Self-citationGenetics of psychosis; insights from views across the genome
O’Donovan, M. C., Craddock, N. J., & Owen, M. J. (2009) · Human Genetics · doi:10.1007/s00439-009-0703-0 · Cited by 216
Toulopoulou, T., Picchioni, M., Rijsdijk, F. V., Hua-Hall, M., Ettinger, U., Sham, P. C., & Murray, R. M. (2008) · Annals of General Psychiatry · doi:10.1186/1744-859x-7-s1-s8 · Cited by 211
Self-citationSubstantial Genetic Overlap Between Neurocognition and Schizophrenia
Toulopoulou, T., Picchioni, M., Rijsdijk, F. V., Hua-Hall, M., Ettinger, U., Sham, P. C., & Murray, R. M. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.12.1348 · Cited by 211
Self-citationFlora, A., Garcia, J. J., Christina Thaller, B., & Zoghbi, H. Y. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707456104 · Cited by 193
Long-term potentiation in the hippocampus
Voronin, L. L. (1983) · Neuroscience · doi:10.1016/0306-4522(83)90099-4 · Cited by 169
A Syndrome of Mental Retardation, Wide Mouth and Intermittent Overbreathing
PITT, D. B., & Hopkins, I. J. (1978) · Journal of Paediatrics and Child Health · doi:10.1111/jpc.1978.14.3.182 · Cited by 127
The dystrobrevin-binding protein 1 gene: features and networks
Guo, A. Y., Sun, J., Riley, B. P., Thiselton, D. L., Kendler, K. S., & Zhao, Z. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.88 · Cited by 100
Kalscheuer, V. M., Feenstra, I., van Ravenswaaij‐Arts, C. M. A., Smeets, D., Menzel, C., Ullmann, R., Musante, L., & Ropers, H. (2008) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32419 · Cited by 78
Broadbelt, K. G., Ramprasaud, A., & Jones, L. B. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2006.04.028 · Cited by 66
N-Methyl-d-aspartate Induces Neurogranin/RC3 Oxidation in Rat Brain Slices
Li, J., Pak, J. H., Huang, F. L., & Huang, K. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.3.1294 · Cited by 60
Association of the gene encoding neurogranin with schizophrenia in males
Ruano, D., Aulchenko, Y. S., Macedo, A., Soares, M. J., Valente, J., Azevedo, M. H., Hutz, M. H., Gama, C. S., Lobato, M. I. R., Belmonte-de-Abreu, P. S., et al. (2006) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2006.10.008 · Cited by 52
Incidence of Schizophrenia in a Nationwide Cohort of Patients With Type 1 Diabetes Mellitus
Juvonen, H., Reunanen, A., Haukka, J. K., Muhonen, M., Suvisaari, J., Arajärvi, R., Partonen, T., & Lönnqvist, J. K. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.8.894 · Cited by 49
Self-citationHuang, F. L., Huang, K., & Boucheron, C. (2007) · Learning & Memory · doi:10.1101/lm.636107 · Cited by 46
Li, T., Underhill, J. A., Liu, X. H., Sham, P. C., Donaldson, P. T., Murray, R. M., Wright, P., & Collier, D. A. (2001) · Schizophrenia Research · doi:10.1016/s0920-9964(00)00111-0 · Cited by 35
Self-citationCaMKII Activation State Underlies Synaptic Labile Phase of LTP and Short-Term Memory Formation
Wang, H., Feng, R., Wang, L. P., Li, F. R., Cao, X., & Tsien, J. Z. (2008) · Current Biology · doi:10.1016/j.cub.2008.08.064 · Cited by 35
Influence of thyroid hormone on brain gene expression.
Bernal, J., Rodríguez‐Peña, A., Ma, I., Ibarrola, N., & Munoz, A. (1992) · PubMed · Cited by 18
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Insel, T., Cuthbert, B., Garvey, M., Heinssen, R., Pine, D. S., Quinn, K., Sanislow, C., & Wang, P. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.09091379 · Cited by 7,067
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821
Schizophrenia risk from complex variation of complement component 4
Sekar, A., Bialas, A. R., de Rivera, H., Davis, A., Hammond, T. R., Kamitaki, N., Tooley, K., Presumey, J., Baum, M., Van Doren, V., et al. (2016) · Nature · doi:10.1038/nature16549 · Cited by 2,394
Benefits and limitations of genome-wide association studies
Tam, V., Patel, N. K., Turcotte, M., Bossé, Y., Paré, G., & Meyre, D. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0127-1 · Cited by 2,208
Metadata
- Authors
- †Genetic Risk and Outcome in Psychosis (GROUP), Stefansson, H., Ophoff, R. A., Steinberg, S., Andreassen, O. A., Cichon, S., Rujescu, D., Werge, T., 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. D., 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., Magnusdottir, B. B., Sigmundsson, T., Olason, P., Masson, G., Gulcher, J. R., Haraldsson, M., Fossdal, R., Thorgeirsson, T. E., Thorsteinsdottir, U., Ruggeri, M., Tosato, S., Franke, B., Strengman, E., Kiemeney, L. A., Melle, I., Djurovic, S., Abramova, L., 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., Cantor, R. M., Murray, R., Kong, A., Golimbet, V., Carracedo, A., Arango, C., Costas, J., Jönsson, E. G., Terenius, L., Agartz, I., Petursson, H., Nöthen, M. M., Rietschel, M., Matthews, P. M., Muglia, P., Peltonen, L., St Clair, D., Goldstein, D. B., Stefansson, K., & Collier, D. A.
- Affiliations
- deCODE Genetics (Iceland) (IS)
- University of Bonn (DE)
- Sankt Hans Hospital (DK)
- Aarhus University Hospital (DK)
- Aarhus University (DK)
- Copenhagen University Hospital (DK)
- Statens Serum Institut (DK)
- Heidelberg University (DE)
- Ludwig-Maximilians-Universität München (DE)
- Semmelweis University (HU)
- University of Verona (IT)
- Radboud University Medical Center (NL)
- University of Oslo (NO)
- Mental Health Research Center of Russian Academy of Medical Sciences (RU)
- King's College London (GB)
- Duke University (US)
- University of California, Los Angeles (US)
- Hospital General Universitario Gregorio Marañón (ES)
- Karolinska Institutet (SE)
- University of Iceland (IS)
- GlaxoSmithKline (United Kingdom) (GB)
- Wellcome Sanger Institute (GB)
- University of Aberdeen (GB)
- ORCID
- Ophoff, Roel A.
- Steinberg, Stacy
- Andreassen, Ole A.
- Cichon, Sven
- Rujescu, Dan
- Werge, Thomas
- Pietiläinen, Olli P. H.
- Mors, Ole
- Mortensen, Preben B.
- Nyegaard, Mette
- Hansen, Thomas
- Suvisaari, Jaana
- Paunio, Tiina
- Børglum, Anders D.
- Hartmann, Annette
- Nordentoft, Merete
- Hougaard, David
- Böttcher, Yvonne
- Olesen, Jes
- Möller, Hans-Jürgen
- Giegling, Ina
- Mattheisen, Manuel
- Bitter, István
- Réthelyi, János M.
- Olason, Pall
- Haraldsson, Magnus
- Thorgeirsson, Thorgeir E.
- Ruggeri, Mirella
- Tosato, Sarah
- Franke, Barbara
- Strengman, Eric
- Kiemeney, Lambertus A.
- Melle, Ingrid
- Djurovic, Srdjan
- Bramon, Elvira
- Vassos, Evangelos
- Ettinger, Ulrich
- Picchioni, Marco
- Need, Anna C.
- Ge, Dongliang
- Freimer, Nelson B.
- Cantor, Rita M.
- Murray, Robin
- Kong, Augustine
- Arango, Celso
- Costas, Javier
- Jönsson, Erik G.
- Terenius, Lars
- Agartz, Ingrid
- Nöthen, Markus M.
- Rietschel, Marcella
- Matthews, Paul M.
- Muglia, Pierandrea
- Peltonen, Leena
- Goldstein, David B.
- Collier, David A.
- Venue
- Nature
- Published
- 2009-07-01
- Volume
- 460
- Issue
- 7256
- Pages
- 744-747
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3077530
- OpenAlex
- W2127205775
- Cited by
- 1,677
- References
- 39
- Citations by year
- 2026: 21 · 2025: 39 · 2024: 47 · 2023: 38 · 2022: 47 · 2021: 65 · 2020: 62 · 2019: 66 · 2018: 56 · 2017: 90 · 2016: 116 · 2015: 148 · 2014: 140 · 2013: 165 · 2012: 196
- FWCI
- 116.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- VU Research Portal (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- GlaxoSmithKline
- Wellcome Trust (089061)
- National Institute for Health and Care Research (PDA/02/06/016)
- Bundesministerium für Bildung und Forschung (NGFN-2)
- Alfried Krupp von Bohlen und Halbach-Stiftung
- National Institutes of Health (6r01hl087679-03)
- National Heart, Lung, and Blood Institute (R01 HL087679, 1-R01HL087679-01)
- National Institute of Mental Health (R01MH078075, MH078075)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- schizophrenia, genetic susceptibility, single nucleotide polymorphisms, copy number variation, major histocompatibility complex, neurogranin, TCF4, immune function, brain development, memory and cognition, mental illness
- MeSH terms
- Transcription Factor 4, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 18, Chromosomes, Human, Pair 6, DNA-Binding Proteins, Genetic Markers, Genotype, Humans, Major Histocompatibility Complex, Schizophrenia, Transcription Factors, Genome, Human, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Neurogranin, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Genome-Wide Association Study
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