Linkage disequilibrium mapping provides further evidence of a gene for reading disability on chromosome 6p21.3-22.
Linkage disequilibrium (LD) mapping was used to follow up reports of linkage between reading disability (RD) and an 18 cM region of chromosome 6p21.3-22. Using a two-stage approach, we tested for association between RD and 22 microsatellite markers in two independent samples of 101 (Stage 1) and 77 (Stage 2) parent/proband trios in which RD was rigorously defined. The most significant replicated associations were observed between combinations of markers D6S109/422/1665 (Stage 1, P=0.002 (adjusted for multiple testing); Stage 2, P=0.0001) and D6S506/1029/1660 (Stage 1, P=0.02 (adjusted), Stage 2, P=0.0001). The only two-marker association observed in both samples was with D6S422/1665 (P=0.01, 0.04). No single marker showed replicated association but D6S506 produced values of P=0.01 and 0.08 which were significant when combined (P=0.02). We observed weaker and less consistent evidence of association in a region of confirmed linkage to RD in previous studies. The most consistently significant haplotypic association D6S109/422/1665, showed association with single-word reading, spelling, phonological awareness, phonological decoding, orthographic accuracy and random automised naming, but not with vocabulary or Attention Deficit Hyperactivity Disorder. Our findings strongly support the presence of a gene contributing to RD in a region of chromosome 6 between markers D6S109 and D6S1260, but do not rule out the presence of a gene between D6S1556 and MOG.
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Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK.
Robinson
L
L
Duke
M
M
Morris
D W
DW
Webb
V
V
Hamshere
M
M
Milham
C
C
Hopkin
E
E
Pound
K
K
Fernando
S
S
Grierson
A
A
Easton
M
M
Williams
N
N
Van Den Bree
M
M
Chowdhury
R
R
Gruen
J
J
Stevenson
J
J
Krawczak
M
M
Owen
M J
MJ
O'Donovan
M C
MC
Williams
J
J
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002896:Chromosomes, Human, Pair 6; D004410:Dyslexia / Q000235:genetics*; D005192:Family Health; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D010641:Phenotype