Copy number variant study of bipolar disorder in Canadian and UK populations implicates synaptic genes. Issue 4 (3rd April 2014)

• Record Type: Journal Article
• Authors: Noor, Abdul; Lionel, Anath C.; Cohen‐Woods, Sarah; Moghimi, Narges; Rucker, James; Fennell, Alanna; Thiruvahindrapuram, Bhooma; Kaufman, Liana; Degagne, Bryan; Wei, John; Parikh, Sagar V.; Muglia, Pierandrea; Forte, Julia; Scherer, Stephen W.; Kennedy, James L.; Xu, Wei; McGuffin, Peter; Farmer, Anne; Strauss, John; Vincent, John B.
• Is Part Of: American journal of medical genetics. Volume 165:Issue 4(2014)
• Page Start: 303
• Page End: 313
• Publication Date: 2014-04-03
• Subjects: Neuropsychiatry -- Periodicals; Medical genetics -- Periodicals; 616.8904205
• DOI: 10.1002/ajmg.b.32232
• Languages: English
• ISSNs: 1552-4841

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmgb32232-sec-0001" sec-type="section"> <p>Genome‐wide single nucleotide polymorphism (SNP) data from 936 bipolar disorder (BD) individuals and 940 psychiatrically healthy comparison individuals of North European descent were analyzed for copy number variation (CNV). Using multiple CNV calling algorithms, and validating using in vitro molecular analyses, we identified CNVs implicating several candidate genes that encode synaptic proteins, such as <italic>DLG1</italic>, <italic>DLG2</italic>, <italic>DPP6</italic>, <italic>NRXN1</italic>, <italic>NRXN2</italic>, <italic>NRXN3</italic>, <italic>SHANK2</italic>, and <italic>EPHA5</italic>, as well as the neuronal splicing regulator <italic>RBFOX1</italic> (<italic>A2BP1</italic>), and neuronal cell adhesion molecule <italic>CHL1</italic>. We have also identified recurrent CNVs on 15q13.3 and 16p11.2‐regions previously reported as risk loci for neuropsychiatric disorders. In addition, we performed CNV analysis of individuals from 215 BD trios and identified de novo CNVs involving the <italic>NRXN1</italic> and <italic>DRD5</italic> genes. Our study provides further evidence of the occasional involvement of genomic mutations in the etiology of BD, however, there is no evidence of an increased burden of CNVs in BD. Further, the identification of CNVs at multiple members of the neurexin gene family in BD individuals, supports the role of synaptic disruption in the etiology of BD. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>