title: Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients.
abstract: BACKGROUND
  Copy number variations (CNV) have become an important source of human genome variability noteworthy to consider when studying genetic susceptibility to complex diseases. As recent studies have found evidences for the potential involvement of CNVs in psychiatric disorders, we have studied the dosage effect of structural genome variants as a possible susceptibility factor for different psychiatric disorders in a candidate gene approach.
  
  
  METHODS
  After selection of 68 psychiatric disorders' candidate genes overlapping with CNVs, MLPA assays were designed to determine changes in copy number of these genes. The studied sample consisted of 724 patients with psychiatric disorders (accounting for anxiety disorders, mood disorders, eating disorders and schizophrenia) and 341 control individuals.
  
  
  RESULTS
  CNVs were detected in 30 out of the 68 genes screened, indicating that a considerable proportion of neuronal pathways genes contain CNVs. When testing the overall burden of rare structural genomic variants in the different psychiatric disorders compared to control individuals, there was no statistically significant difference in the total amount of gains and losses. However, 14 out of the 30 changes were only found in psychiatric disorder patients but not in control individuals. These genes include GRM7, previously associated to major depression disorder and bipolar disorder, SLC6A13, in anxiety disorders, and S100B, SSTR5 and COMT in schizophrenia.
  
  
  CONCLUSIONS
  Although we have not been able to found a clear association between the studied CNVs and psychiatric disorders, the rare variants found only within the patients could account for a step further towards understanding the pathophysiology of psychiatric disorders.
authors.affiliation: CIBER en Epidemiología y Salud Pública (CIBERESP), Genes and Disease Program, Center for Genomic Regulation (CRG-UPF), Barcelona 08003, Catalonia, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Saus
authors.forename: Anna
authors.initials: A
authors.lastname: Brunet
authors.forename: Lluís
authors.initials: L
authors.lastname: Armengol
authors.forename: Pino
authors.initials: P
authors.lastname: Alonso
authors.forename: José M
authors.initials: JM
authors.lastname: Crespo
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernández-Aranda
authors.forename: Miriam
authors.initials: M
authors.lastname: Guitart
authors.forename: Rocío
authors.initials: R
authors.lastname: Martín-Santos
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Menchón
authors.forename: Ricard
authors.initials: R
authors.lastname: Navinés
authors.forename: Virginia
authors.initials: V
authors.lastname: Soria
authors.forename: Marta
authors.initials: M
authors.lastname: Torrens
authors.forename: Mikel
authors.initials: M
authors.lastname: Urretavizcaya
authors.forename: Vicenç
authors.initials: V
authors.lastname: Vallès
authors.forename: Mònica
authors.initials: M
authors.lastname: Gratacòs
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
mesh_terms: D000328:Adult; D000368:Aged; D001008:Anxiety Disorders / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D056915:DNA Copy Number Variations; D039721:Diagnostic and Statistical Manual of Mental Disorders; D001068:Feeding and Eating Disorders / Q000235:genetics; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics; D009434:Neural Pathways / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics; D016133:Polymerase Chain Reaction; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics; D017481:Receptors, Somatostatin / Q000235:genetics; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018094:Receptors, Metabotropic Glutamate; D017481:Receptors, Somatostatin; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C493418:SLC6A13 protein, human; C099323:cortistatin; C094573:somatostatin receptor 5; D002394:Catechol O-Methyltransferase