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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 ORCID:, Milham, C, Hopkin, E, Pound, K, Fernando, S, Grierson, A, Easton, M, Williams, Nigel Melville ORCID:, van den Bree, Marianne Bernadette ORCID:, Chowdhury, R, Gruen, J, Stevenson, J, Krawczak, M, Owen, Michael John ORCID:, O'Donovan, Michael Conlon ORCID: and Williams, Julie ORCID: 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/

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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)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
Publisher: Nature Publishing Group
ISSN: 1359-4184
Last Modified: 16 Apr 2024 03:55

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