title: Identification of rare high-risk copy number variants affecting the dopamine transporter gene in mental disorders.
abstract: BACKGROUND
  The dopamine transporter, also known as solute carrier 6A3 (SLC6A3), plays an important role in synaptic transmission by regulating the reuptake of dopamine in the synapses. In line with this, variations in the gene encoding this transporter have been linked to both schizophrenia and affective disorders. Recently, copy number variants (CNVs) in SLC6A3 have been identified in healthy subjects but so far, the implication of CNVs affecting this gene in psychiatric diseases has not been addressed.
  
  
  OBJECTIVE
  In the present study, we aimed to investigate whether CNVs affecting SLC6A3 represent rare high-risk variants of psychiatric disorders.
  
  
  METHODS
  We performed a systematic screening for CNVs affecting SLC6A3 in 761 healthy controls, 672 schizophrenia patients, and 194 patients with bipolar disorder in addition to 253 family members from six large pedigrees affected by mental disorders using single nucleotide polymorphism arrays and subsequent verification by real-time polymerase chain reaction.
  
  
  RESULTS
  We identified two duplications and one deletion affecting SLC6A3 in the patients, while no such CNVs were identified in any of the controls. The identified CNVs were of different sizes and two affected several genes in addition to SLC6A3.
  
  
  CONCLUSIONS
  Our findings suggest that rare high-risk CNVs affecting the gene encoding the dopamine transporter contribute to the pathogenesis of schizophrenia and affective disorders.
authors.affiliation: a Louise K. Hoeffding , Institute of Biological Psychiatry , Mental Health Centre Sct. Hans, Mental Health Services Copenhagen , Denmark ;
authors.forename: Louise K
authors.initials: LK
authors.lastname: Hoeffding
authors.affiliation: b Linh T.T. Duong , Institute of Biological Psychiatry , Mental Health Centre Sct. Hans, Mental Health Services Copenhagen , Denmark ;
authors.forename: Linh T T
authors.initials: LT
authors.lastname: Duong
authors.affiliation: c Andrés Ingason , deCODE Genetics , Reykjavik , Iceland ;
authors.forename: Andrés
authors.initials: A
authors.lastname: Ingason
authors.affiliation: d Anders Rosengren , Institute of Biological Psychiatry , Mental Health Centre Sct. Hans, Mental Health Services Copenhagen , Denmark ;
authors.forename: Anders
authors.initials: A
authors.lastname: Rosengren
authors.affiliation: e Ester Sorbanski , Department of Psychiatry and Psychotherapy , Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg , Mannheim , Germany ;
authors.forename: Ester
authors.initials: E
authors.lastname: Sorbanski
authors.affiliation: f Stephanie H. Witt , Department of Genetic Epidemiology in Psychiatry , Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg , Mannheim , Germany ;
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Witt
authors.affiliation: g Srdjan Djurovic , Department of Medical Genetics , Oslo University Hospital , Oslo , Norway , and NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Norway ;
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.affiliation: h Ole A. Andreassen , Department of Medical Genetics , Oslo University Hospital , Oslo , Norway , and NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Norway ;
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.affiliation: i Thomas Hansen , Institute of Biological Psychiatry , Mental Health Centre Sct. Hans, Mental Health Services Copenhagen , Denmark ;
authors.forename: Thomas
authors.initials: T
authors.lastname: Hansen
authors.affiliation: j Thomas Werge , Institute of Biological Psychiatry , Mental Health Centre Sct. Hans, Mental Health Services Copenhagen , Denmark , Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark, and Department of Clinical Medicine, University of Copenhagen, Denmark ;
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.affiliation: k Henrik B. Rasmussen , Institute of Biological Psychiatry , Mental Health Centre Sct. Hans, Mental Health Services Copenhagen , Denmark.
authors.forename: Henrik B
authors.initials: HB
authors.lastname: Rasmussen
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics; D056915:DNA Copy Number Variations; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins
keywords: Affective disorders; copy number variants; dopamine transporter; schizophrenia; solute carrier 6A3.