Analysis of t(9;17)(q33.2;q25.3) chromosomal breakpoint regions and genetic association reveals novel candidate genes for bipolar disorder
Open accessAbstract
Objectives: Breakpoints of chromosomal abnormalities facilitate identification of novel candidate genes for psychiatric disorders. Genome‐wide significant evidence supports the linkage between chromosome 17q25.3 and bipolar disorder ( BD ). Co‐segregation of translocation t(9;17)(q33.2;q25.3) with psychiatric disorders has been reported. We aimed to narrow down these chromosomal breakpoint regions and to investigate the associations between single nucleotide polymorphisms within these regions and BD as well as schizophrenia ( SZ ) in large genome‐wide association study samples. Methods: We cross‐linked Danish psychiatric and cytogenetic case registers to identify an individual with both t(9;17)(q33.2;q25.3) and BD . Fluorescent in situ hybridization was employed to map the chromosomal breakpoint regions of this proband. We accessed the Psychiatric Genomics Consortium BD (n = 16,731) and SZ (n = 21,856) data. Genetic associations between these disorders and single nucleotide polymorphisms within these breakpoint regions were analysed by BioQ, FORGE , and Regulome DB programmes. Results: Four protein‐coding genes [coding for (endonuclease V ( ENDOV ) , neuronal pentraxin I ( NPTX 1 ), ring finger protein 213 ( RNF 213 ), and regulatory‐associated protein of mammalian target of rapamycin (mTOR) ( RPTOR )] were found to be located within the 17q25.3 breakpoint region. NPTX 1 was significantly associated with BD (p = 0.004) , while ENDOV was significantly associated with SZ (p = 0.0075) after Bonferroni correction. Conclusions: Prior linkage evidence and our findings suggest NPTX 1 as a novel candidate gene for BD .
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Chromosomal breakpoint analysis in patients with BD suggested NPTX1 as a novel candidate gene for BD.
“Chromosomal breakpoint analysis in patients with BD suggested NPTX1 as a novel candidate gene for BD (Rajkumar et al. 2015).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Rajkumar et al. 2015
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- Authors
- Rajkumar, A. P., Christensen, J. H., Mattheisen, M., Jacobsen, I., Bache, I., Pallesen, J., Grove, J., Qvist, P., McQuillin, A., Gurling, H. M., Tümer, Z., Mors, O., & Børglum, A. D.
- Affiliations
- Aarhus University (DK)
- University of Copenhagen (DK)
- University College London (GB)
- Copenhagen University Hospital (DK)
- Corresponding author
- Rajkumar, Anto P
- ORCID
- Venue
- Bipolar Disorders
- Publisher
- Wiley
- Published
- 2014-07-23
- Volume
- 17
- Issue
- 2
- Pages
- 205-211
- ISSN
- 1398-5647 (ISSN-L)
- 1399-5618
- OpenAlex
- W1993539939
- Cited by
- 24
- References
- 41
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 1
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- Locations
- Bipolar Disorders (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- The Danish Council for Independent Research | Medical Sciences. (NA)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- bipolar disorder, schizophrenia, candidate genes, NPTX1, RNF213, RPTOR, single nucleotide polymorphisms, genetic association
- MeSH terms
- Regulatory-Associated Protein of mTOR, Pentraxins, Adenosine Triphosphatases, Bipolar Disorder, C-Reactive Protein, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 9, Family, Humans, Genetic Linkage, Nerve Tissue Proteins, Schizophrenia, Translocation, Genetic, In Situ Hybridization, Fluorescence, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Deoxyribonuclease (Pyrimidine Dimer), Ubiquitin-Protein Ligases, Adaptor Proteins, Signal Transducing, Genome-Wide Association Study
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