Evidence for a language quantitative trait locus on chromosome 7q in multiplex autism families

Am J Hum Genet. 2002 Jan;70(1):60-71. doi: 10.1086/338241. Epub 2001 Dec 6.


Autism is a syndrome characterized by deficits in language and social skills and by repetitive behaviors. We hypothesized that potential quantitative trait loci (QTLs) related to component autism endophenotypes might underlie putative or significant regions of autism linkage. We performed nonparametric multipoint linkage analyses, in 152 families from the Autism Genetic Resource Exchange, focusing on three traits derived from the Autism Diagnostic Interview: "age at first word," "age at first phrase," and a composite measure of "repetitive and stereotyped behavior." Families were genotyped for 335 markers, and multipoint sib pair linkage analyses were conducted. Using nonparametric multipoint linkage analysis, we found the strongest QTL evidence for age at first word on chromosome 7q (nonparametric test statistic [Z] 2.98; P=.001), and subsequent linkage analyses of additional markers and association analyses in the same region supported the initial result (Z=2.85, P=.002; chi(2)=18.84, df 8, P=.016). Moreover, the peak fine-mapping result for repetitive behavior (Z=2.48; P=.007) localized to a region overlapping this language QTL. The putative autism-susceptibility locus on chromosome 7 may be the result of separate QTLs for the language and repetitive or stereotyped behavior deficits that are associated with the disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autistic Disorder / complications
  • Autistic Disorder / genetics*
  • Autistic Disorder / physiopathology
  • Chromosome Mapping
  • Chromosomes, Human / genetics
  • Chromosomes, Human, Pair 7 / genetics*
  • Female
  • Humans
  • Language Development Disorders / complications
  • Language Development Disorders / genetics*
  • Language Development Disorders / physiopathology
  • Lod Score
  • Male
  • Mental Disorders / complications
  • Mental Disorders / genetics
  • Mental Disorders / physiopathology
  • Nuclear Family
  • Quantitative Trait, Heritable*
  • Software
  • Statistics, Nonparametric