title: Identification of genetic loci underlying the phenotypic constructs of autism spectrum disorders.
abstract: OBJECTIVE
  To investigate the underlying phenotypic constructs in autism spectrum disorders (ASD) and to identify genetic loci that are linked to these empirically derived factors.
  
  
  METHODS
  Exploratory factor analysis was applied to two datasets with 28 selected Autism Diagnostic Interview-Revised (ADI-R) algorithm items. The first dataset was from the Autism Genome Project (AGP) phase I (1,236 ASD subjects from 618 families); the second was from the AGP phase II (804 unrelated ASD subjects). Variables derived from the factor analysis were then used as quantitative traits in genome-wide variance components linkage analyses.
  
  
  RESULTS
  Six factors, namely, joint attention, social interaction and communication, nonverbal communication, repetitive sensory-motor behavior, peer interaction, and compulsion/restricted interests, were retained for both datasets. There was good agreement between the factor loading patterns from the two datasets. All factors showed familial aggregation. Suggestive evidence for linkage was obtained for the joint attention factor on 11q23. Genome-wide significant evidence for linkage was obtained for the repetitive sensory-motor behavior factor on 19q13.3.
  
  
  CONCLUSIONS
  This study demonstrates that the underlying phenotypic constructs based on the ADI-R algorithm items are replicable in independent datasets, and that the empirically derived factors are suitable and informative in genetic studies of ASD.
authors.affiliation: University of Manitoba, Canada.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Liu
authors.forename: Stelios
authors.initials: S
authors.lastname: Georgiades
authors.forename: Eric
authors.initials: E
authors.lastname: Duku
authors.forename: Ann
authors.initials: A
authors.lastname: Thompson
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Cook
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Wijsman
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
authors.forename: Peter
authors.initials: P
authors.lastname: Szatmari
mesh_terms: D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology* / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005163:Factor Analysis, Statistical; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009656:North America / Q000453:epidemiology; D010641:Phenotype; D040641:Quantitative Trait Loci