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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, Marian Lindsay, Milham, C, Hopkin, E, Pound, K, Fernando, S, Grierson, A, Easton, M, Williams, Nigel Melville, van den Bree, Marianne Bernadette, Chowdhury, R, Gruen, J, Stevenson, J, Krawczak, M, Owen, Michael John, O'Donovan, Michael Conlon and Williams, Julie 2003. Linkage disequilibrium mapping provides further evidence of a gene for reading disability on chromosome 6p21.3-22. Molecular Psychiatry 8 (2) , pp. 176-185. 10.1038/sj.mp.4001216

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
Publisher: Nature Publishing Group
ISSN: 1359-4184
Last Modified: 25 Nov 2017 00:45
URI: http://orca.cf.ac.uk/id/eprint/82706

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