Evidence for linkage and association with reading disability on 6p21.3-22.
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.
Kaplan
D E
DE
Yale Child Health Research Center, Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-8081, USA.
Gayán
J
J
Ahn
J
J
Won
T-W
TW
Pauls
D
D
Olson
R K
RK
DeFries
J C
JC
Wood
F
F
Pennington
B F
BF
Page
G P
GP
Smith
S D
SD
Gruen
J R
JR
D000293:Adolescent; D000483:Alleles; D002648:Child; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004200:Diseases in Twins / Q000235:genetics; D004410:Dyslexia / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D019655:Quantitative Trait, Heritable; D020080:Tandem Repeat Sequences / Q000235:genetics
D005819:Genetic Markers