A major susceptibility locus for specific language impairment is located on 13q21

Am J Hum Genet. 2002 Jul;71(1):45-55. doi: 10.1086/341095. Epub 2002 Jun 4.


Children who fail to develop language normally-in the absence of explanatory factors such as neurological disorders, hearing impairment, or lack of adequate opportunity-are clinically described as having specific language impairment (SLI). SLI has a prevalence of approximately 7% in children entering school and is associated with later difficulties in learning to read. Research indicates that genetic factors are important in the etiology of SLI. Studies have consistently demonstrated that SLI aggregates in families. Increased monozygotic versus dizygotic twin concordance rates indicate that heredity, not just shared environment, is the cause of the familial clustering. We have collected five pedigrees of Celtic ancestry that segregate SLI, and we have conducted genomewide categorical linkage analysis, using model-based LOD score techniques. Analysis was conducted under both dominant and recessive models by use of three phenotypic classifications: clinical diagnosis, language impairment (spoken language quotient <85) and reading discrepancy (nonverbal IQ minus non-word reading >15). Chromosome 13 yielded a maximum multipoint LOD score of 3.92 under the recessive reading discrepancy model. Simulation to correct for multiple models and multiple phenotypes indicated that the genomewide empirical P value is <.01. As an alternative measure, we also computed the posterior probability of linkage (PPL), obtaining a PPL of 53% in the same region. One other genomic region yielded suggestive results on chromosome 2 (multipoint LOD score 2.86, genomic P value <.06 under the recessive language impairment model). Our findings underscore the utility of traditional LOD-score-based methods in finding genes for complex diseases, specifically, SLI.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autistic Disorder / genetics
  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 13 / genetics*
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 2 / genetics
  • Female
  • Genes, Recessive
  • Genotype
  • Humans
  • Language Development Disorders / genetics*
  • Lod Score
  • Male
  • Models, Genetic
  • Pedigree
  • Phenotype

Associated data

  • OMIM/209850
  • OMIM/602081
  • OMIM/606354