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

Turic, D., Robinson, L., Duke, M., Morris, D.W., Webb, V., Hamshere, M., Milham, C., Hopkin, E., Pound, K., Fernando, S., Grierson, A., Easton, M., Williams, N., Van Den Bree, M., Chowdhury, R., Gruen, J., Stevenson, J., Krawczak, M., Owen, M.J., O'Donovan, M.C and Williams, J. (2003) Linkage disequilibrium mapping provides further evidence of a gene for reading disability on chromosome 6p21.3-22. Molecular Psychiatry, 8 (2), 176-185. (doi:10.1038/sj.mp.4001216).

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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