title: Analysis of t(9;17)(q33.2;q25.3) chromosomal breakpoint regions and genetic association reveals novel candidate genes for bipolar disorder.
abstract: OBJECTIVE
  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 RegulomeDB programmes.
  
  
  RESULTS
  Four protein-coding genes [coding for (endonuclease V (ENDOV), neuronal pentraxin I (NPTX1), ring finger protein 213 (RNF213), and regulatory-associated protein of mammalian target of rapamycin (mTOR) (RPTOR)] were found to be located within the 17q25.3 breakpoint region. NPTX1 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 NPTX1 as a novel candidate gene for BD.
authors: Department of Biomedicine, Institute of Human Genetics, Aarhus University, Aarhus, Denmark; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
authors: Anto P
authors: AP
authors: Rajkumar
authors: Jane H
authors: JH
authors: Christensen
authors: Manuel
authors: M
authors: Mattheisen
authors: Iben
authors: I
authors: Jacobsen
authors: Iben
authors: I
authors: Bache
authors: Jonatan
authors: J
authors: Pallesen
authors: Jakob
authors: J
authors: Grove
authors: Per
authors: P
authors: Qvist
authors: Andrew
authors: A
authors: McQuillin
authors: Hugh M
authors: HM
authors: Gurling
authors: Zeynep
authors: Z
authors: Tümer
authors: Ole
authors: O
authors: Mors
authors: Anders D
authors: AD
authors: Børglum
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000251:Adenosine Triphosphatases; D001714:Bipolar Disorder / Q000235:genetics*; D002097:C-Reactive Protein / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000235:genetics*; D005190:Family; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000076223:Regulatory-Associated Protein of mTOR; D012559:Schizophrenia / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D000099153:Pentraxins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D002097:C-Reactive Protein; D043224:Deoxyribonuclease (Pyrimidine Dimer); D009419:Nerve Tissue Proteins; D000076223:Regulatory-Associated Protein of mTOR; D044767:Ubiquitin-Protein Ligases; D000099153:Pentraxins; C463659:RPTOR protein, human; C557998:RNF213 protein, human
keywords: NPTX1; RPTOR; bipolar disorder; genetic association studies; genetic translocation