title: Genetic risk variants for dyslexia on chromosome 18 in a German cohort.
abstract: Dyslexia is characterized by impaired reading and spelling. The disorder has a prevalence of about 5% in Germany, and a strong hereditary component. Several loci are thought to be involved in the development of dyslexia. Scerri et al. identified eight potential dyslexia-associated single nucleotide polymorphisms (SNPs) in seven genes on chromosome 18 in an English-speaking population. Here, we present an association analysis that explores the relevance of these SNPs in a German population comprising 388 dyslexia cases and 364 control cases. In case-control analysis, three nominal SNP associations were replicated. The major alleles of NEDD4L-rs12606138 and NEDD4L-rs8094327 were risk associated [odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.0-1.7, P-value = 0.017 and OR = 1.39, 95% CI = 1.1-1.7, P-value = 0.007, respectively], and both SNPs were in strong linkage disequilibrium (r(2)  = 0.95). For MYO5B-rs555879, the minor allele was risk associated (OR = 1.31, 95% CI = 1.1-1.6, P-value = 0.011). The combined analysis of SNP sets using set enrichment analysis revealed a study-wide significant association for three SNPs with susceptibility for dyslexia. In summary, our results substantiate genetic markers in NEDD4L and MYO5B as risk factors for dyslexia and provide first evidence that the relevance of these markers is not restricted to the English language.
authors.affiliation: Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology.
authors.forename: B
authors.initials: B
authors.lastname: Mueller
authors.forename: P
authors.initials: P
authors.lastname: Ahnert
authors.forename: J
authors.initials: J
authors.lastname: Burkhardt
authors.forename: J
authors.initials: J
authors.lastname: Brauer
authors.forename: I
authors.initials: I
authors.lastname: Czepezauer
authors.forename: E
authors.initials: E
authors.lastname: Quente
authors.forename: J
authors.initials: J
authors.lastname: Boltze
authors.forename: A
authors.initials: A
authors.lastname: Wilcke
authors.forename: H
authors.initials: H
authors.lastname: Kirsten
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D004410:Dyslexia / Q000235:genetics*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D008297:Male; D018995:Myosin Heavy Chains / Q000235:genetics; D024701:Myosin Type V / Q000235:genetics; D000075702:Nedd4 Ubiquitin Protein Ligases; D020641:Polymorphism, Single Nucleotide; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; C505832:MYO5B protein, human; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618485:Nedd4L protein, human; D044767:Ubiquitin-Protein Ligases; D024701:Myosin Type V; D018995:Myosin Heavy Chains
keywords: Chromosome 18; German primary school students; dyslexia; genetic association studies; genetic predisposition to disease; linkage disequilibrium; quantitative association study; replication study; single nucleotide polymorphism