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Genetic risk variants for dyslexia on chromosome 18 in a German cohort
Authors:B. Mueller  P. Ahnert  J. Burkhardt  J. Brauer  I. Czepezauer  E. Quente  J. Boltze  H. Kirsten
Affiliation:1. Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology;2. Institute for Medical Informatics, Statistics, and Epidemiology;3. LIFE Center (Leipzig Interdisciplinary Research Cluster of Genetic Factors, Phenotypes, and Environment), Universit?t Leipzig;4. Translational Centre for Regenerative Medicine (TRM), Universit?t Leipzig;5. Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, , Leipzig, Germany;6. Stroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital and Harvard Medical School, , Boston, MA, USA
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 .
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
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