title: Linkage disequilibrium mapping provides further evidence of a gene for reading disability on chromosome 6p21.3-22.
abstract: 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.
authors.affiliation: Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK.
authors.forename: D
authors.initials: D
authors.lastname: Turic
authors.forename: L
authors.initials: L
authors.lastname: Robinson
authors.forename: M
authors.initials: M
authors.lastname: Duke
authors.forename: D W
authors.initials: DW
authors.lastname: Morris
authors.forename: V
authors.initials: V
authors.lastname: Webb
authors.forename: M
authors.initials: M
authors.lastname: Hamshere
authors.forename: C
authors.initials: C
authors.lastname: Milham
authors.forename: E
authors.initials: E
authors.lastname: Hopkin
authors.forename: K
authors.initials: K
authors.lastname: Pound
authors.forename: S
authors.initials: S
authors.lastname: Fernando
authors.forename: A
authors.initials: A
authors.lastname: Grierson
authors.forename: M
authors.initials: M
authors.lastname: Easton
authors.forename: N
authors.initials: N
authors.lastname: Williams
authors.forename: M
authors.initials: M
authors.lastname: Van Den Bree
authors.forename: R
authors.initials: R
authors.lastname: Chowdhury
authors.forename: J
authors.initials: J
authors.lastname: Gruen
authors.forename: J
authors.initials: J
authors.lastname: Stevenson
authors.forename: M
authors.initials: M
authors.lastname: Krawczak
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.forename: M C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: J
authors.initials: J
authors.lastname: Williams
mesh_terms: 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