title: Polymorphisms in the 13q33.2 gene G72/G30 are associated with childhood-onset schizophrenia and psychosis not otherwise specified.
abstract: BACKGROUND
  Childhood-onset schizophrenia (COS), defined as onset of psychotic symptoms by age 12 years, is a rare and severe form of the disorder that seems to be clinically and neurobiologically continuous with the adult disorder.
  
  
  METHODS
  We studied a rare cohort consisting of 98 probands; 71 of these probands received a DSM-defined diagnosis of schizophrenia, and the remaining 27 were diagnosed as psychosis not otherwise specified (NOS) (upon 2-6 year follow-up, 13 have subsequently developed bipolar disorder). Two overlapping genes, G72 and G30 on 13q33.2, were identified through linkage-disequilibrium-based positional cloning. Single nucleotide polymorphisms (SNPs) at the G72/G30 locus were independently associated with both bipolar illness and schizophrenia. We analyzed SNPs at this locus with a family-based transmission disequilibrium test (TDT) and haplotype analyses for the discrete trait, as well as quantitative TDT for intermediate phenotypes, using the 88 probands (including COS and psychosis-NOS) with parental participation.
  
  
  RESULTS
  We observed significant pairwise and haplotype associations between SNPs at the G72/G30 locus and psychotic illness. Furthermore, these markers showed associations with scores on a premorbid phenotype measured by the Autism Screening Questionnaire, and with age of onset.
  
  
  CONCLUSIONS
  These findings, although limited by potential referral bias, confirm and strengthen previous reports that G72/G30 is a susceptibility locus both for schizophrenia and bipolar disorder.
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1600, USA.
authors.forename: Anjené M
authors.initials: AM
authors.lastname: Addington
authors.forename: Michele
authors.initials: M
authors.lastname: Gornick
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Sporn
authors.forename: Nitin
authors.initials: N
authors.lastname: Gogtay
authors.forename: Deanna
authors.initials: D
authors.lastname: Greenstein
authors.forename: Marge
authors.initials: M
authors.lastname: Lenane
authors.forename: Peter
authors.initials: P
authors.lastname: Gochman
authors.forename: Natalie
authors.initials: N
authors.lastname: Baker
authors.forename: Rishi
authors.initials: R
authors.lastname: Balkissoon
authors.forename: Radha Krishna
authors.initials: RK
authors.lastname: Vakkalanka
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
authors.forename: Richard E
authors.initials: RE
authors.lastname: Straub
authors.forename: Judith L
authors.initials: JL
authors.lastname: Rapoport
mesh_terms: D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D015331:Cohort Studies; D005192:Family Health; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015810:Linkage Disequilibrium; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000235:genetics*; D012561:Schizophrenia, Childhood / Q000235:genetics*; D011795:Surveys and Questionnaires
chemical_list: D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins