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Linkage disequilibrium mapping provides further evidence of a gene for reading disability on chromosome 6p21.3–22

Molecular Psychiatry volume 8, pages 176–185 (2003)Cite this article

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.

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Acknowledgements

We gratefully acknowledge the support of the Wellcome Trust (Grant no. 054171) and the University of Wales PhD scheme for funding this research. Julie Williams, Michael O'Donovan and Michael Owen are also supported by a Medical Research Council Co-operative Group Grant (Grant no. G9810900). Michael Krawczak holds a Heisenberg grant from the Deutsche-Forschungsgemeinschaft (Grant no. Kr 1093/5-2).

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  1. D Turic, M Duke and J Gruen: Equal contributors

Authors and Affiliations

  1. Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK

    D Turic, L Robinson, M Duke, D W Morris, V Webb, M Hamshere, C Milham, E Hopkin, K Pound, S Fernando, A Grierson, M Easton, N Williams, M Van Den Bree, M Krawczak, M J Owen, M C O'Donovan & J Williams

  2. Department of Neuroscience and Cognitive Development, Babraham Institute, Babraham, Cambridge, UK

    R Chowdhury

  3. Yale Child Health Research Center, OA464 Congress Avenue, New Haven, USA

    J Gruen

  4. Centre for Research into Psychological Development, University of Southampton, Southampton, UK

    J Stevenson

  5. Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK

    M Krawczak

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Turic, D., Robinson, L., Duke, M. et al. Linkage disequilibrium mapping provides further evidence of a gene for reading disability on chromosome 6p21.3–22. Mol Psychiatry 8, 176–185 (2003). https://doi.org/10.1038/sj.mp.4001216

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