Further evidence for DYX1C1 as a susceptibility factor for dyslexia

Faten Dahdouh · Heidi Anthoni · Isabel Tapia‐Páez · Myriam Peyrard‐Janvid · Gerd Schulte‐Körne · Andreas Warnke +7 more

70 citations0/0 files storedPsychiatric Genetics

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Reading and Literacy Development Language Development and Disorders Genetic Associations and Epidemiology

Abstract

OBJECTIVE: Dyslexia-susceptibility-1-candidate-1 (DYX1C1) was the first gene associated with dyslexia. Since the original report of 2003, eight replication attempts have been published reporting discordant results. As the dyslexia community still considers the role of DYX1C1 unsettled, we explored the contribution of this gene in a sample of 366 trios of German descent. METHODS: To the common four markers used in previous studies, we added two new single nucleotide polymorphisms found by resequencing both the putative regulatory and coding region of the gene in randomly selected cases and controls. As linkage disequilibrium blocks of the region were not easy to define, we approached the association problem by running a transmission disequilibrium test over sliding windows of dimension 1 to 6 on consecutive markers. The significance of this test was calculated generating the empirical distribution of the global P value by simulating the data. As our study sample had a large female proband content, we also stratified our analysis by sex. RESULTS: We found statistically significant association with global corrected P value of 0.036. The three-marker haplotype G/G/G spanning rs3743205/rs3743204/rs600753 was most associated with a P value of 0.006 and odds ratio 3.7 (95% confidence interval: 1.4-9.6) in female probands. A detailed haplotype-phenotype analysis revealed that the dyslexia subphenotype short-term memory contributed mainly to the observed findings. This is in accordance with a recent short-term memory-DYX1C1 association in an independent sample of dyslexia. CONCLUSION: As significant association was proved in our sample, we could also conclude that denser maps, sex information, and well-defined subphenotypes are crucial to correctly determine the contribution of DYX1C1 to dyslexia.

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References

2004Sex Differences in Developmental Reading Disability 2003A candidate gene for developmental dyslexia encodes a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain 2001Incidence of Reading Disability in a Population-Based Birth Cohort, 1976–1982, Rochester, Minn 2005Strong Genetic Evidence of DCDC2 as a Susceptibility Gene for Dyslexia 2005Genetic influences on early word recognition abilities and disabilities: a study of 7‐year‐old twins 2007Genetics of dyslexia: the evolving landscape 2006Genes, cognition and dyslexia: learning to read the genome 2004Support for EKN1 as the susceptibility locus for dyslexia on 15q21

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