title: Mutation burden of rare variants in schizophrenia candidate genes.
abstract: BACKGROUND
  Schizophrenia (SCZ) is a very heterogeneous disease that affects approximately 1% of the general population. Recently, the genetic complexity thought to underlie this condition was further supported by three independent studies that identified an increased number of damaging de novo mutations DNM in different SCZ probands. While these three reports support the implication of DNM in the pathogenesis of SCZ, the absence of overlap in the genes identified suggests that the number of genes involved in SCZ is likely to be very large; a notion that has been supported by the moderate success of Genome-Wide Association Studies (GWAS).
  
  
  METHODS
  To further examine the genetic heterogeneity of this disease, we resequenced 62 genes that were found to have a DNM in SCZ patients, and 40 genes that encode for proteins known to interact with the products of the genes with DNM, in a cohort of 235 SCZ cases and 233 controls.
  
  
  RESULTS
  We found an enrichment of private nonsense mutations amongst schizophrenia patients. Using a kernel association method, we were able to assess for association for different sets. Although our power of detection was limited, we observed an increased mutation burden in the genes that have DNM.
authors.affiliation: McGill University and Genome Quebec Innovation Center, McGill University, Montréal, Canada; Montreal Neurological Institute and Hospital, Department of Neurology and Neurosurgery, McGill University, Montréal, Canada.
authors.forename: Simon L
authors.initials: SL
authors.lastname: Girard
authors.affiliation: Montreal Neurological Institute and Hospital, Department of Neurology and Neurosurgery, McGill University, Montréal, Canada; Université de Montréal, Faculty of Medicine, Montréal, Canada; Département de pathologie et biologie cellulaire, Université de Montréal, Montreal, Canada.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Dion
authors.affiliation: Montreal Neurological Institute and Hospital, Department of Neurology and Neurosurgery, McGill University, Montréal, Canada.
authors.forename: Cynthia V
authors.initials: CV
authors.lastname: Bourassa
authors.affiliation: Centre de Pharmacogénomique Beaulieu-Saucier, Institut de Cardiologie de Montréal, Montreal, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Geoffroy
authors.affiliation: Université de Montréal, Faculty of Medicine, Montréal, Canada.
authors.forename: Pamela
authors.initials: P
authors.lastname: Lachance-Touchette
authors.affiliation: Centre de Pharmacogénomique Beaulieu-Saucier, Institut de Cardiologie de Montréal, Montreal, Canada.
authors.forename: Amina
authors.initials: A
authors.lastname: Barhdadi
authors.affiliation: Centre de Pharmacogénomique Beaulieu-Saucier, Institut de Cardiologie de Montréal, Montreal, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Langlois
authors.affiliation: Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, Canada.
authors.forename: Ridha
authors.initials: R
authors.lastname: Joober
authors.affiliation: Université Paris Descartes, Faculté de Médecine Paris Descartes, Paris, France; INSERM U894, Laboratoire de Physiopathologie des Maladies Psychiatriques, Paris, France; Service Hospitalo Universitaire, Centre Hospitalier Sainte-Anne, 7 rue Cabanis, 75014 Paris, France.
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Krebs
authors.affiliation: Centre de Pharmacogénomique Beaulieu-Saucier, Institut de Cardiologie de Montréal, Montreal, Canada; Université de Montréal, Faculty of Medicine, Montréal, Canada.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dubé
authors.affiliation: Montreal Neurological Institute and Hospital, Department of Neurology and Neurosurgery, McGill University, Montréal, Canada.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000328:Adult; D000465:Algorithms; D016022:Case-Control Studies; D050881:E1A-Associated p300 Protein / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D048308:Mitogen-Activated Protein Kinase 14 / Q000235:genetics*; D059645:Mutation Rate; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology
chemical_list: D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D048308:Mitogen-Activated Protein Kinase 14