Further evidence for DYX1C1 as a susceptibility factor for dyslexia.
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.


CONCLUSIONS
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.
Dahdouh
Faten
F
Institute of Human Genetics, Life and Brain Center, University of Bonn, Bonn, Germany.
Anthoni
Heidi
H
Tapia-Páez
Isabel
I
Peyrard-Janvid
Myriam
M
Schulte-Körne
Gerd
G
Warnke
Andreas
A
Remschmidt
Helmut
H
Ziegler
Andreas
A
Kere
Juha
J
Müller-Myhsok
Bertram
B
Nöthen
Markus M
MM
Schumacher
Johannes
J
Zucchelli
Marco
M
D003598:Cytoskeletal Proteins; D004410:Dyslexia / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*
D003598:Cytoskeletal Proteins; C478878:DNAAF4 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins