title: Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems.
abstract: OBJECTIVE
  : Recently, molecular cytogenetic techniques have identified novel copy number variants in individuals with schizophrenia. However, no large-scale prospective studies have been performed to characterize the broader spectrum of phenotypes associated with such copy number variants in individuals with unexplained physical and intellectual disabilities encountered in a diagnostic setting.
  
  
  METHODS
  : We analyzed 38,779 individuals referred to our diagnostic laboratory for microarray testing for the presence of copy number variants encompassing 20 putative schizophrenia susceptibility loci. We also analyzed the indications for study for individuals with copy number variants overlapping those found in six individuals referred for schizophrenia.
  
  
  RESULTS
  : After excluding larger gains or losses that encompassed additional genes outside the candidate loci (e.g., whole-arm gains/losses), we identified 1113 individuals with copy number variants encompassing schizophrenia susceptibility loci and 37 individuals with copy number variants overlapping those present in the six individuals referred to our laboratory for schizophrenia. Of these, 1035 had a copy number variant of one of six recurrent loci: 1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11, and 22q11.2. The indications for study for these 1150 individuals were diverse and included developmental delay, intellectual disability, autism spectrum, and multiple congenital anomalies.
  
  
  CONCLUSIONS
  : The results from our study, the largest genotype-first analysis of schizophrenia susceptibility loci to date, suggest that the phenotypic effects of copy number variants associated with schizophrenia are pleiotropic and imply the existence of shared biologic pathways among multiple neurodevelopmental conditions.
authors.affiliation: Signature Genomic Laboratories, 2820 N. Astor St., Spokane, WA 99207, USA. shaffer@signaturegenomics.com
authors.forename: Trilochan
authors.initials: T
authors.lastname: Sahoo
authors.forename: Aaron
authors.initials: A
authors.lastname: Theisen
authors.forename: Jill A
authors.initials: JA
authors.lastname: Rosenfeld
authors.forename: Allen N
authors.initials: AN
authors.lastname: Lamb
authors.forename: J Britt
authors.initials: JB
authors.lastname: Ravnan
authors.forename: Roger A
authors.initials: RA
authors.lastname: Schultz
authors.forename: Beth S
authors.initials: BS
authors.lastname: Torchia
authors.forename: Nicholas
authors.initials: N
authors.lastname: Neill
authors.forename: Ian
authors.initials: I
authors.lastname: Casci
authors.forename: Bassem A
authors.initials: BA
authors.lastname: Bejjani
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
mesh_terms: D000293:Adolescent; D001526:Behavioral Symptoms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D058674:Chromosome Duplication; D002877:Chromosomes, Human; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007805:Language Development Disorders / Q000235:genetics*; D008297:Male; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult