Copy number variant study of bipolar disorder in Canadian and UK populations implicates synaptic genes

Am J Med Genet B Neuropsychiatr Genet. 2014 Jun;165B(4):303-13. doi: 10.1002/ajmg.b.32232. Epub 2014 Apr 3.


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 DLG1, DLG2, DPP6, NRXN1, NRXN2, NRXN3, SHANK2, and EPHA5, as well as the neuronal splicing regulator RBFOX1 (A2BP1), and neuronal cell adhesion molecule CHL1. 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 NRXN1 and DRD5 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.

Keywords: NRXN1; bipolar disorder; copy number variant; synapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bipolar Disorder / genetics*
  • Calcium-Binding Proteins
  • Canada
  • Case-Control Studies
  • Cell Adhesion Molecules, Neuronal / genetics
  • DNA Copy Number Variations / genetics*
  • Humans
  • Nerve Tissue Proteins / genetics
  • Neural Cell Adhesion Molecules
  • Reproducibility of Results
  • Synapses / genetics*
  • United Kingdom
  • Young Adult


  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal
  • NRXN1 protein, human
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecules