Analysis of t(9;17)(q33.2;q25.3) chromosomal breakpoint regions and genetic association reveals novel candidate genes for bipolar disorder. (23rd July 2014)

• Record Type: Journal Article
• Authors: Rajkumar, Anto P; Christensen, Jane H; Mattheisen, Manuel; Jacobsen, Iben; Bache, Iben; Pallesen, Jonatan; Grove, Jakob; Qvist, Per; McQuillin, Andrew; Gurling, Hugh M; Tümer, Zeynep; Mors, Ole; Børglum, Anders D
• Is Part Of: Bipolar disorders. Volume 17:Number 2(2015)
• Page Start: 205
• Page End: 211
• Publication Date: 2014-07-23
• Subjects: Manic-depressive illness -- Periodicals; Depression, Mental -- Periodicals; 616.895
• DOI: 10.1111/bdi.12239
• Languages: English
• ISSNs: 1398-5647

Abstract

<abstract abstract-type="main" id="bdi12239-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bdi12239-sec-0001" sec-type="section"> <title>Objectives</title> <p>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.</p> </sec> <sec id="bdi12239-sec-0002" sec-type="section"> <title>Methods</title> <p>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 <italic>in situ</italic> 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.</p> </sec> <sec id="bdi12239-sec-0003" sec-type="section"> <title>Results</title> <p>Four protein‐coding genes [coding for (endonuclease V (<italic>ENDOV</italic>), neuronal pentraxin I (<italic>NPTX1</italic>), ring finger protein 213 (<italic>RNF213</italic>), and regulatory‐associated protein of mammalian target of rapamycin (mTOR) (<italic>RPTOR</italic>)] were found to be located within the 17q25.3 breakpoint region. <italic>NPTX1</italic> was significantly associated with BD (p = 0.004), while <italic>ENDOV</italic> was significantly associated with SZ (p = 0.0075) after Bonferroni correction.</p> </sec> <sec id="bdi12239-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Prior linkage evidence and our findings suggest <italic>NPTX1</italic> as a novel candidate gene for BD.</p> </sec> </abstract>