Association between schizophrenia and common variation in neurocan (NCAN), a genetic risk factor for bipolar disorder
Abstract
A recent study found genome-wide significant association between common variation in the gene neurocan (NCAN, rs1064395) and bipolar disorder (BD). In view of accumulating evidence that BD and schizophrenia partly share genetic risk factors, we tested this single-nucleotide polymorphism for association with schizophrenia in three independent patient-control samples of European ancestry, totaling 5061 patients and 9655 controls. The rs1064395 A-allele, which confers risk for BD, was significantly over-represented in schizophrenia patients compared to controls (p=2.28×10(-3); odds ratio=1.11). Follow-up in non-overlapping samples from the Schizophrenia Psychiatric GWAS Consortium (5537 patients, 8043 controls) provided further support for our finding (p=0.0239, odds ratio=1.07). Our data suggest that genetic variation in NCAN is a common risk factor for BD and schizophrenia.
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CSPGs are involved in the pathophysiology of schizophrenia.
“Emerging evidence from human postmortem, animal model and genetic studies points to their involvement in the pathophysiology of schizophrenia (SZ).1, 2, 3, 4, 5, 6, 7”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [6]
Polymorphisms of genes encoding for several CSPGs have been associated with schizophrenia.
“Finally, polymorphisms of genes encoding for several CSPGs have been associated with SZ.5, 6, 7”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [6]
Genetic vulnerabilities in CSPG genes such as PTPRZ1 and neurocan may reduce CSPG synthesis in schizophrenia.
“In addition, recently reported genetic vulnerabilities for CSPG genes, including PTPRZ1 and neurocan (Buxbaum et al., 2008; Muhleisen et al., 2012; Ripke and Schizophrenia Working Group of the Psychiatric Genomics, 2014), may contribute to decrease CSPG synthesis in SZ.”
From Losing the sugar coating: Potential impact of perineuronal net abnormalities on interneurons in schizophrenia (2015) · cites this paper as Muhleisen et al., 2012
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- Authors
- Mühleisen, T. W., Mattheisen, M., Strohmaier, J., Degenhardt, F., Priebe, L., Schultz, C. C., Breuer, R., Meier, S., Hoffmann, P., Rivandeneira, F., Hofman, A., Uitterlinden, A. G., Moebus, S., Gieger, C., Emeny, R., Ladwig, K.-H., Wichmann, H.-E., Schwarz, M., Kammerer-Ciernioch, J., Schlösser, R. G. M., Nenadic, I., Sauer, H., Mössner, R., Maier, W., Rujescu, D., Lange, C., Ophoff, R. A., Schulze, T. G., Rietschel, M., Nöthen, M. M., & Cichon, S.
- Affiliations
- University of Bonn (DE)
- Central Institute of Mental Health (DE)
- Friedrich Schiller University Jena (DE)
- Erasmus MC (NL)
- University of Duisburg-Essen (DE)
- Helmholtz Munich (DE)
- TUM Klinikum (DE)
- Ludwig-Maximilians-Universität München (DE)
- University of California, Los Angeles (US)
- Universitätsmedizin Göttingen (DE)
- Corresponding author
- Cichon, Sven
- ORCID
- Mühleisen, Thomas W.
- Mattheisen, Manuel
- Strohmaier, Jana
- Degenhardt, Franziska
- Hoffmann, Per
- Uitterlinden, André G.
- Moebus, Susanne
- Gieger, Christian
- Emeny, Rebecca
- Ladwig, Karl-Heinz
- Wichmann, H.-Erich
- Schwarz, Markus
- Sauer, Heinrich
- Rujescu, Dan
- Lange, Christoph
- Ophoff, Roel A.
- Schulze, Thomas G.
- Rietschel, Marcella
- Nöthen, Markus M.
- Cichon, Sven
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 138
- Issue
- 1
- Pages
- 69-73
- ISSN
- 0920-9964 (ISSN-L)
- OpenAlex
- W2060248929
- Cited by
- 80
- References
- 26
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2022: 4 · 2021: 3 · 2020: 10 · 2019: 4 · 2018: 11 · 2017: 6 · 2016: 4 · 2015: 8 · 2014: 10 · 2013: 10 · 2012: 2
- FWCI
- 6.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Schizophrenia Research (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- JuSER (Forschungszentrum Jülich) (submittedVersion)
- Lirias (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- DZNE Pub (submittedVersion)
- GRO (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (U01HL089856)
- National Institute of Mental Health (R01 MH61675, U01-MH79470, R01MH087590, R01 MH-59571, R01MH59588, U01MH46276, R01MH081862, R01-MH59566, R01-MH60879, U01MH046276, R01-MH60870, R01-MH59586, R01MH059566, R01 MH81800, R01MH59587, U01MH046318, R01-MH59565, R01MH059571, R01MH060879, R01MH059565, U01MH46289, R01MH081800, R01 MH-67257, R01MH060870, U01MH046289, U01MH079469, R01MH061675, R01MH078075, R01MH059586, R01MH059588, R01MH067257, U01MH079470, U01MH46318, R01MH059587, U01MH-79469)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- schizophrenia, neurocan
- MeSH terms
- Bipolar Disorder, Gene Frequency, Genotype, Humans, Nerve Tissue Proteins, Chondroitin Sulfate Proteoglycans, Schizophrenia, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Lectins, C-Type, Neurocan
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