Copy number variant study of bipolar disorder in Canadian and UK populations implicates synaptic genes.
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.
Molecular Neuropsychiatry & Development Lab, Campbell Family Mental Health Research Institute, The Centre for Addiction & Mental Health, Toronto, Ontario, Canada.
Abdul
A
Noor
Anath C
AC
Lionel
Sarah
S
Cohen-Woods
Narges
N
Moghimi
James
J
Rucker
Alanna
A
Fennell
Bhooma
B
Thiruvahindrapuram
Liana
L
Kaufman
Bryan
B
Degagne
John
J
Wei
Sagar V
SV
Parikh
Pierandrea
P
Muglia
Julia
J
Forte
Stephen W
SW
Scherer
James L
JL
Kennedy
Wei
W
Xu
Peter
P
McGuffin
Anne
A
Farmer
John
J
Strauss
John B
JB
Vincent
D001714:Bipolar Disorder / Q000235:genetics*; D002135:Calcium-Binding Proteins; D002170:Canada; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics; D019006:Neural Cell Adhesion Molecules; D015203:Reproducibility of Results; D013569:Synapses / Q000235:genetics*; D006113:United Kingdom; D055815:Young Adult
D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules
NRXN1; bipolar disorder; copy number variant; synapse