Evidence for linkage and association with reading disability on 6p21.3-22

Am J Hum Genet. 2002 May;70(5):1287-98. doi: 10.1086/340449. Epub 2002 Apr 10.


Reading disability (RD), or dyslexia, is a common heterogeneous syndrome with a large genetic component. Several studies have consistently found evidence for a quantitative-trait locus (QTL) within the 17 Mb (14.9 cM) that span D6S109 and D6S291 on chromosome 6p21.3-22. To characterize further linkage to the QTL, to define more accurately the location and the effect size, and to identify a peak of association, we performed Haseman-Elston and DeFries-Fulker linkage analyses, as well as transmission/disequilibrium, total-association, and variance-components analyses, on 11 quantitative reading and language phenotypes. One hundred four families with RD were genotyped with a new panel of 29 markers that spans 9 Mb of this region. Linkage results varied widely in degree of statistical significance for the different linkage tests, but multipoint analysis suggested a peak near D6S461. The average 6p QTL heritability for the 11 reading and language phenotypes was 0.27, with a maximum of 0.66 for orthographic choice. Consistent with the region of linkage described by these studies and others, there was a peak of transmission disequilibrium with a QTL centered at JA04 (chi2=9.48; empirical P=.0033; orthographic choice), and there was strong evidence for total association at this same marker (chi2=11.49; P=.0007; orthographic choice). Although the boundaries of the peak could not be precisely defined, the most likely location of the QTL is within a 4-Mb region surrounding JA04.

Publication types

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

MeSH terms

  • Adolescent
  • Alleles
  • Child
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 6 / genetics*
  • Diseases in Twins / genetics
  • Dyslexia / genetics*
  • Genetic Markers / genetics
  • Genotype
  • Humans
  • Linkage Disequilibrium / genetics
  • Quantitative Trait, Heritable
  • Tandem Repeat Sequences / genetics


  • Genetic Markers