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Genetic risk variants for dyslexia on chromosome 18 in a German cohort

机译:德国队列中18号染色体上阅读障碍的遗传风险变异

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摘要

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.
机译:阅读障碍的特征是阅读和拼写受损。该病在德国的患病率约为5%,并且是很强的遗传成分。几个位点被认为与阅读障碍有关。 Scerri等。在讲英语的人群中,在18号染色体上的七个基因中发现了八种潜在的阅读障碍相关单核苷酸多态性(SNP)。在这里,我们提出了一项关联分析,以探讨这些SNP在德国人群中的相关性,其中包括388个阅读障碍病例和364个对照病例。在病例对照分析中,复制了三个名义SNP关联。 NEDD4L-rs12606138和NEDD4L-rs8094327的主要等位基因是与风险相关的[几率(OR)= 1.35,95%置信区间(CI)= 1.0-1.7,P值= 0.017和OR = 1.39,95%CI = 1.1 –1.7,P值分别== 0.007],并且两个SNP均处于强连锁不平衡状态(r2 == 0.95)。对于MYO5B-rs555879,次要等位基因与风险相关(OR = 1.31,95%CI = 1.1-1.6,P值= 0.011)。使用集富集分析对SNP集进行组合分析,发现在整个研究范围内,三种SNP与诵读困难症的易感性相关。总而言之,我们的研究结果证实了NEDD4L和MYO5B中的遗传标记是诵读困难的危险因素,并提供了第一个证据证明这些标记的相关性不仅限于英语。

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