TDT-association analysis of EKN1 and dyslexia in a Colorado twin cohort
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A candidate gene, EKN1, was recently described in a cohort from Finland for the dyslexia locus on chromosome 15q, DYX1. This report described a (2;15) (q11;21) translocation disrupting EKN1 that cosegregated with dyslexia in a two-generation family. It also characterized a sequence polymorphism in the 5′ untranslated region and a missense mutation that showed significant association in 109 dyslexics compared to 195 controls (p=0.002 and p=0.006, respectively). To confirm these results we interrogated the same polymorphisms in a cohort of 150 nuclear families with dyslexia ascertained through the Colorado Learning Disabilities Research Center. Using QTDT analysis with nine individual quantitative tasks and two composite measures of reading performance, we could not replicate the reported association. We conclude that the polymorphisms identified in the Finland sample are unlikely to be functional DNA changes contributing to dyslexia, and that if variation in EKN1 is causal such changes are more likely to be in regulatory regions that were not sequenced in this study. Alternatively, the published findings of association with markers in EKN1 may reflect linkage disequilibrium with variation in another gene(s) in the region.
Support for JRG and HM is from the Charles H. Hood Foundation (Boston, MA), The Robert Leet and Clara Guthrie Patterson Trust (Hartford, CT), and NIH R01 NS43530. Support for MH is from NIH R01 NS43530. The Colorado Learning Disability Research Center (SDS, RKO, BFP, JCD) is funded by NIH-NICHD 5P50HD027802 to J.C. DeFries, and SDS and BFG were further funded by NIH-NICHD RO1 HD-NS34812.
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