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Free keywords:
Chromosome 18; Dyslexia; Genetic association studies; Genetic predisposition to disease; German primary school students; Linkage disequilibrium; Quantitative association study; Replication study; Single nucleotide polymorphism
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 (r2 = 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.
