1. ¹Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK
2. ²Department of Neuroscience and Cognitive Development, Babraham Institute, Babraham, Cambridge, UK
3. ³Yale Child Health Research Center, OA464 Congress Avenue, New Haven, USA
4. ⁴Centre for Research into Psychological Development, University of Southampton, Southampton, UK
5. ⁵Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK

Correspondence: Prof. J Williams/Prof. M O'Donovan, Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK. E-mail: willamsj@cardiff ac.uk

^*Equal contributors

Received 7 February 2002; Revised 10 April 2002; Accepted 6 May 2002.

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.